ORCID Profile
0000-0002-7111-6735
Current Organisations
University of Western Australia
,
Telethon Kids Institute
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Animal Developmental and Reproductive Biology | Biomedical Instrumentation | Nanotechnology | Nanobiotechnology |
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Technology
Publisher: Springer Science and Business Media LLC
Date: 25-03-2014
DOI: 10.1007/S00737-014-0422-Y
Abstract: Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an emerging literature associating low levels of 25(OH)-vitamin D with depressive symptoms. However, the link between 25(OH)-vitamin D status in pregnancy and altered risk of postnatal depressive symptoms has not been examined. We hypothesise that low levels of 25(OH)-vitamin D in maternal serum during pregnancy will be associated with a higher incidence of postpartum depressive symptoms. We prospectively collected sera at 18 weeks gestation from 796 pregnant women in Perth (1989-1992) who were enrolled in the Western Australian Pregnancy Cohort (Raine) Study and measured levels of 25(OH)-vitamin D. Women reported postnatal depressive symptoms at 3 days post-delivery. Women in the lowest quartile for 25(OH)-vitamin D status were more likely to report a higher level of postnatal depression symptoms than women who were in the highest quartile for vitamin D, even after accounting for a range of confounding variables including season of birth, body mass index and sociodemographic factors. Low vitamin D during pregnancy is a risk factor for the development of postpartum depression symptoms.
Publisher: Cold Spring Harbor Laboratory
Date: 02-03-2021
DOI: 10.1101/2021.03.02.433510
Abstract: Brown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little known is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPC) – which give rise to DCs – in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low-dose ultraviolet radiation (UVR) significantly reduced the ‘whitening’ effect of eating a high-fat diet upon interscapular (i)BAT of mice. Here, we examined whether this observation may be linked to changes in the phenotype of HSPC and myeloid-derived immune cells in iBAT and bone marrow of mice using 12-colour flow cytometry. Many HSPC subsets declined in both iBAT and bone marrow with increasing metabolic dysfunction. Conversely, with rising adiposity and metabolic dysfunction, conventional (c)DCs increased in both of these tissues. When compared to low-fat diet, consumption of high-fat diet significantly reduced proportions of myeloid, common myeloid and megakaryocyte-erythrocyte progenitors in iBAT, and short-term hematopoietic stem cells in bone marrow. In mice fed a high-fat diet, exposure to low-dose UVR significantly reduced proportions of cDCs in iBAT, independently of nitric oxide release from irradiated skin (blocked using the scavenger, cPTIO), but did not significantly modify HSPC subsets in either tissue. Further studies are needed to determine whether changes in these cell populations contribute towards metabolic dysfunction.
Publisher: Wiley
Date: 15-06-2010
Publisher: Elsevier
Date: 2007
Publisher: Frontiers Media SA
Date: 09-11-2022
DOI: 10.3389/FENVS.2022.970658
Abstract: Type-2 diabetes is a leading cause of death and disability. Emerging evidence suggests that ultraviolet radiation or sun exposure may limit its development. We used freely available online datasets to evaluate the associations between solar radiation and type-2 diabetes prevalence across Australia. We extracted prevalence data for 1822 postcodes from the Australian Diabetes Map on 25 January 2020. Daily solar radiation data averaged over 30-years (1990–2019) were collated from online databases (Australian Bureau of Meteorology). Population-weighted linear regression models were adjusted for covariates at the postcode level including socioeconomic status (IRSAD), remoteness, mean age, gender, Aboriginal and Torres Strait Islander status, as well as mean annual ambient temperature (1961–1990) and rainfall (1981–2010). A consistent inverse correlation was observed between type-2 diabetes prevalence and solar radiation, after adjusting for these covariates (ß (coefficient of regression) = −0.045 95% CI: −0.086, −0.0051 p = 0.027). However, the relative contribution of solar radiation towards type-2 diabetes prevalence was small (2.1%) in this model. Other significant correlations between type-2 diabetes prevalence and covariates included: socioeconomic status (ß = −0.017 95% CI: −0.017, −0.016 p & 0.001), mean age (ß = 0.041 95% CI: 0.028, 0.054 p & 0.015), remoteness (ß = −0.05 95% CI: −0.088, −0.011 p & 0.001) and rainfall (ß = −0.0008 95% CI: −0.00097, −0.00067 p & 0.001). In conclusion, in Australian postcodes, higher levels of solar radiation and rainfall was associated with reduced type-2 diabetes prevalence. Further studies are needed that consider lifestyle covariates such as physical activity.
Publisher: Wiley
Date: 07-05-2010
Publisher: American Thoracic Society
Date: 11-2015
Publisher: Frontiers Media SA
Date: 23-12-2020
Abstract: During the COVID-19 (coronavirus disease of 2019) pandemic, researchers have been seeking low-cost and accessible means of providing protection from its harms, particularly for at-risk in iduals such as those with cardiovascular disease, diabetes and obesity. One possible way is via safe sun exposure, and/or dietary supplementation with induced beneficial mediators (e.g., vitamin D). In this narrative review, we provide rationale and updated evidence on the potential benefits and harms of sun exposure and ultraviolet (UV) light that may impact COVID-19. We review recent studies that provide new evidence for any benefits (or otherwise) of UV light, sun exposure, and the induced mediators, vitamin D and nitric oxide, and their potential to modulate morbidity and mortality induced by infection with SARS-CoV-2 (severe acute respiratory disease coronavirus-2). We identified substantial interest in this research area, with many commentaries and reviews already published however, most of these have focused on vitamin D, with less consideration of UV light (or sun exposure) or other mediators such as nitric oxide. Data collected to-date suggest that ambient levels of both UVA and UVB may be beneficial for reducing severity or mortality due to COVID-19, with some inconsistent findings. Currently unresolved are the nature of the associations between blood 25-hydroxyvitamin D and COVID-19 measures, with more prospective data needed that better consider lifestyle factors, such as physical activity and personal sun exposure levels. Another short-coming has been a lack of measurement of sun exposure, and its potential to influence COVID-19 outcomes. We also discuss possible mechanisms by which sun exposure, UV light and induced mediators could affect COVID-19 morbidity and mortality, by focusing on likely effects on viral pathogenesis, immunity and inflammation, and potential cardiometabolic protective mechanisms. Finally, we explore potential issues including the impacts of exposure to high dose UV radiation on COVID-19 and vaccination, and effective and safe doses for vitamin D supplementation.
Publisher: JMIR Publications Inc.
Date: 16-03-2022
DOI: 10.2196/35137
Abstract: A balanced approach toward sun exposure and protection is needed by young people. Excessive sun exposure increases their risk for skin cancers such as melanoma, whereas some exposure is necessary for vitamin D and healthy bones. We have developed a new iOS smartphone app—Sun Safe—through a co-design process, which aims to support healthy and balanced decision-making by young teenagers (aged 12-13 years). The aim of this study was to test the capacity of Sun Safe to improve sun health knowledge and behaviors of young teenagers in 3 pilot intervention studies completed in 2020. Young teenagers (aged 12-13 years N=57) were recruited through the web or through a local school via an open-access website and given access to Sun Safe (29/57, 51%) or a placebo (SunDial) app (28/57, 49%). Participants completed sun health questionnaires and knowledge quizzes before and after the 6-week intervention (either on the web or in class) and rated the quality of the app they used via a survey. Of the 57 participants, 51 (89%) participants (26, 51% for placebo arm and 25, 49% for the Sun Safe arm) completed these studies, with most ( %) reporting that they used a smartphone to access their designated app either “once a fortnight” or “once/twice in total.” Improved sun health knowledge—particularly about the UV Index—was observed in participants who were given access to Sun Safe compared with those who used the placebo (−6.2 [percentage correct] difference in predicted means, 95% CI –12.4 to –0.03 P=.049 2-way ANOVA). Unexpectedly, there were significantly more sunburn events in the Sun Safe group (relative risk 1.7, 95% CI 1.1-1.8 P=.02 Fisher exact test), although no differences in time spent outdoors or sun-protective behaviors were reported. COVID-19 pandemic–related community-wide shutdowns during April 2020 (when schools were closed) reduced the time spent outdoors by minutes per day (–105 minutes per day difference in predicted means, 95% CI –150 to –59 minutes per day P=.002 paired 2-tailed Student t test). Sun Safe was well-rated by participants, particularly for information (mean 4.2, SD 0.6 out of 5). Access to the Sun Safe app increased sun health knowledge among young teenagers in these pilot intervention studies. Further investigations with larger s le sizes are required to confirm these observations and further test the effects of Sun Safe on sun-protective behaviors.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2015
DOI: 10.1007/S00011-015-0868-Z
Abstract: During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2021
DOI: 10.1038/S41598-021-84881-8
Abstract: Altered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS). However, the immunomodulatory actions of SCFAs and intermediaries in their ability to influence MS pathogenesis are uncertain. In this study, levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood s les taken at first presentation of Clinically Isolated Syndrome (CIS an early form of MS) or MS and compared to healthy controls. There was a small but significant reduction in propionate levels in the serum of patients with CIS or MS compared with healthy controls. The frequencies of circulating T follicular regulatory cells and T follicular helper cells were significantly positively correlated with serum levels of propionate. Levels of butyrate associated positively with frequencies of IL-10-producing B-cells and negatively with frequencies of class-switched memory B-cells. TNF production by polyclonally-activated B-cells correlated negatively with acetate levels. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS.
Publisher: Microbiology Society
Date: 05-2006
Abstract: As with human cytomegalovirus (HCMV) infection of humans, murine CMV (MCMV) infection is widespread in its natural host, the house mouse Mus domesticus , and may consist of mixed infection with different CMV isolates. The incidence and mechanisms by which mixed infection occurs in free-living mice are unknown. This study used two approaches to determine whether mixed infection with MCMV could be established in laboratory mice. The first utilized two naturally occurring MCMV strains, N1 and G4, into which the lacZ gene was inserted by homologous recombination. The lacZ gene was used to track recombinant and parental viruses in simultaneously coinfected mice. In the second approach, a real-time quantitative PCR (qPCR) assay was used to detect viral immediate-early 1 ( ie1 ) gene sequences in mice successively coinfected with G4 and then with the K181 MCMV strain. In both systems, mixed infection was detected in the salivary glands and lungs of experimentally infected mice. MCMV-specific antibody in sera and G4 IE1-specific cytotoxic lymphocyte responses in the spleens of twice-infected mice did not prevent reinfection. Finally, the prevalence of mixed infection in free-living mice trapped in four Australian locations was investigated using real-time qPCR to detect ie1 DNA sequences of N1, G4 and K181. Mixed infection with MCMVs containing the G4 and K181 ie1 sequences was detected in the salivary glands of 34·2 % of trapped mice. The observations that mixed infections are common in free-living M. domesticus and are acquired by immunocompetent mice through simultaneous or successive infections are important for vaccine development.
Publisher: Wiley
Date: 19-04-2010
DOI: 10.1111/J.1365-2222.2010.03469.X
Abstract: In human asthma, and experimental allergic airways disease in mice, antigen-presenting cells and CD4(+) effector cells at the airway mucosa orchestrate, and CD4(+)CD25(+) regulatory T cells attenuate, allergen immunity. UV irradiation of skin before sensitization with ovalbumin (OVA) causes significantly reduced asthma-like responses in respiratory tissues. To determine whether UV-induced changes in CD11c(+) cells, CD4(+)CD25(+) effector cells or CD4(+)CD25(+) regulatory cells in the trachea and airway draining lymph nodes (ADLNs) were responsible for reduced allergic airways disease. The phenotype and function of CD11c(+) cells and CD4(+)CD25(+) cells in the trachea and ADLNs of UV- and non-irradiated, OVA-sensitized mice was examined 24 h after a single exposure to aerosolized OVA. No changes in the function of CD11c(+) cells from UV-irradiated mice were observed. CD4(+)CD25(+) cells from UV-irradiated, OVA-sensitized mice harvested 24 h after OVA aerosol proliferated less in response to OVA in vitro and were unable to suppress the proliferation of OVA-sensitized responder cells. This result suggested reduced activation of effector T cells in the airway mucosa of UV-irradiated, OVA-sensitized mice. To exclude regulatory cells of any type, there was similar proliferation in vivo to aerosolized OVA by CFSE-loaded, OVA-TCR-specific CD4(+) cells adoptively transferred into UV- and non-irradiated, OVA-sensitized mice. In addition, there was no difference in the expression of regulatory T cell markers (Foxp3, IL-10, TGF-beta mRNA). To examine effector T cells, ADLN cells from UV-irradiated, OVA-sensitized and -challenged mice were cultured with OVA. There was reduced expression of the early activation marker CD69 by CD4(+)CD25(+) cells, and reduced proliferation in the absence of the regulatory cytokine, IL-10. Reduced allergic airways disease in UV-irradiated mice is due to fewer effector CD4(+)CD25(+) cells in the trachea and ADLNs, and not due to UV-induced regulatory cells.
Publisher: Bioscientifica
Date: 04-2021
DOI: 10.1530/JOE-20-0487
Abstract: In this narrative review, we provide an overview of the role of physical activity as part of differing exposomes (our combined non-genetic exposures from conception onwards) and environmental influences on metabolic health. We discuss ‘beneficial’ exposomes (green/natural outdoor spaces, sun exposure, healthy diets and features of built environments) that could synergise with physical activity to prevent metabolic dysfunction, particularly that related to lifestyle diseases of obesity, type 2 diabetes and metabolic syndrome. Physical activity may also reduce the capacity of some adverse exposomes, specifically those with significant levels of air pollution, to contribute towards metabolic dysfunction. Other exposomes, such as those experienced during pandemics (including COVID-19), potentially limit opportunities for physical activity, and there may be unexpected combined effects of physical activity with other infections (e.g. adenovirus-36) on metabolic health. Finally, we discuss how environments could be better optimised to create exposomes that promote the health benefits of physical activity and likely future directions of this research field.
Publisher: Wiley
Date: 28-10-2013
DOI: 10.1111/IMM.12145
Publisher: Wiley
Date: 03-2014
DOI: 10.1002/PHY2.276
Publisher: Springer Science and Business Media LLC
Date: 11-02-2019
Publisher: Wiley
Date: 24-08-2019
DOI: 10.1111/PHP.13145
Abstract: Obesity is a significant health problem worldwide. Exposure to low-dose ultraviolet radiation (like that in sunlight) suppresses the development of obesity in mice however, the nature of the associations between sun exposure and adiposity is not well understood in humans. The present study characterized cross-sectional relationships between sun exposure and adiposity in a convenience cohort of breast (n = 269 mean age = 58 years) and prostate (n = 78 mean age = 69 years) cancer patients. Participants were enrolled in a 3-month exercise program in Perth, Australia. Self-reported questionnaires measured time spent outdoors (previous week, winter and summer), sex, age, treatment received and physical activity levels. Adiposity measures included body mass index, waist-hip ratio and body fat percentage (measured via DXA). In unadjusted models, greater time spent outdoors across all times was significantly associated with lower waist-hip ratio, while greater time spent outdoors in the last winter was associated with lower body fat percentage, but not when stratified by sex. There were no statistically significant associations between time spent outdoors and adiposity after adjusting for sex, age, treatments received and physical activity. Longitudinal studies in larger populations may elucidate significant associations not found in our study due to the cross-sectional design and power limitations.
Publisher: Brill | Wageningen Academic
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 14-03-2021
DOI: 10.1186/S12931-021-01681-4
Abstract: An amendment to this paper has been published and can be accessed via the original article.
Publisher: MDPI AG
Date: 18-12-2016
Publisher: Springer Science and Business Media LLC
Date: 08-09-2021
DOI: 10.1186/S13104-021-05764-9
Abstract: This study aimed to explore current attitudes towards sun protection, and sun-seeking behaviour among young Australian adolescents. It was done as part of a larger project aiming to develop a digital resource to support young people in making informed sun-health decisions. Ten (4 male, 6 female) adolescents (12–13 years of age) living in Perth (Western Australia) were recruited through a social media-based strategy. Each participant engaged in a semi-structured telephone interview which explored their sun-health decision-making, with interview transcripts assessed qualitatively using NVivo. Three major themes (and eight sub-themes) were identified: (1) ‘personal sun health considerations’ (2) ‘attitudes towards sun protection’ and (3) ‘recommendations’. The importance of sun protection was appreciated by participants. However, females were more diligent in the use of sun protection while males were indifferent. Behaviours were influenced by parental input, the school environment and engagement in sport. Adolescents had limited knowledge of the UV Index and its implications for sun protection, and the health importance of sun-derived vitamin D. Overall, the importance of sun protection was acknowledged but did not consistently translate into sun protective behaviours.
Publisher: Australasian Association for Clinical Biochemistry and Laboratory Medicine
Date: 28-08-2019
Abstract: Emerging findings suggest that exposure to ultraviolet wavelengths of sunlight modulates metabolic function. Here we review the metabolic effects of exposure to ultraviolet radiation (UVR), focusing on the effects of phototherapies (that administer UVR), and advice to increase sun exposure in in iduals enrolled in clinical trials and intervention studies. We identified 25 studies in which the effects of UVR on metabolic outcomes were examined, including: narrowband ultraviolet B phototherapy (nbUVB, n = 12) psoralen ultraviolet A phototherapy (n = 4) other types of UVR phototherapy (n = 5) and sun exposure advice (n = 5). Most studies recruited a small number of participants (≤100), who were middle-aged in iduals undergoing treatment for psoriasis flare, with phototherapy or sun exposure advice administered for ≤12 weeks. Data obtained at baseline were usually compared with an endpoint following treatment with UVR, for a limited number of outcomes. There were few studies in which markers of glucose metabolism were assessed, with some beneficial effects of sun exposure (but not phototherapy) reported. LDL-cholesterol levels were lower in in iduals receiving sun exposure advice, while treatment with nbUVB reduced blood concentrations of inflammatory markers (C-reactive protein and interleukin-6). Future studies should focus on determining whether the effects of these interventions change with time, and if they are dependent on the source of UVR (i.e. phototherapy or sun exposure) and wavelength(s) of light administered. Furthermore, studies need to measure a variety of (clinical) markers of glucose metabolism, adiposity and inflammation, control for factors such as skin type and sex, and stratify participants for metabolic disease diagnosis.
Publisher: Wiley
Date: 17-04-2018
DOI: 10.1111/IMCB.12050
Abstract: Asthma is a chronic disease affecting up to 10% of the Australian population for which medical treatment is solely aimed at relief of symptoms rather than prevention of disease. Evidence from animal and human studies demonstrates a strong link between viral respiratory infections, atopy and the development of asthma. Type I IFNs include IFNα and IFNβ, with subtype expression tailored toward the specific viral infection. We hypothesized that exposure to type I IFNs and allergen may interfere with the healthy response to innocuous airway antigen exposure. In this study, we use an ovalbumin (OVA)-induced BALB/c model of experimental allergic airways disease, where pre-exposure of the airways to OVA is protective against allergen sensitization, leading to allergen tolerance. We investigated airways pre-exposure with OVA and type I IFNs on development of allergic airways disease. We demonstrate restoration of allergic airways disease on pre-exposure with allergen and IFNβ, and not IFNα. Dysfunction in tolerance led to changes in dendritic cell antigen capture/traffic, T-cell and B-cell responses. Furthermore, exposure to IFNβ with ongoing allergen exposure led to the development of hallmark asthma features, including OVA-specific IgE and airways eosinophilia. Data indicate a role for IFNβ in linking viral infection and allergy.
Publisher: Wiley
Date: 27-01-2012
DOI: 10.1111/J.1399-3038.2011.01146.X
Abstract: There is debate as to whether vitamin D deficiency contributes towards the extent of the asthma epidemic. In this study, using a mouse model, we determined whether vitamin D deficiency in utero and during early life modulated the severity of asthma. Using dietary restriction, vitamin D(3) -replete and vitamin D(3) -deficient colonies of BALB/c mice were established. Utilizing the allergic airway disease model of asthma with the experimental allergen ovalbumin (OVA), we examined asthma-like responses 24 h after airway challenge with OVA in adult offspring born to vitamin D(3) -replete and vitamin D(3) -deficient mothers. The ability of airway-draining lymph node cells to proliferate and secrete cytokines in response to OVA ex vivo was significantly enhanced by vitamin D(3) deficiency. However, other aspects of allergic disease, including the numbers and proportions of inflammatory cells and cytokines in the lungs and the quantity of OVA-specific IgE in serum, were not modified. These results suggest that vitamin D(3) deficiency modulates the capacity of lymphocytes to respond to allergens.
Publisher: Faculty Opinions Ltd
Date: 12-2014
DOI: 10.12703/P6-118
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/1426503
Abstract: Skin inflammatory responses in in iduals with allergic dermatitis may be suppressed by dietary vitamin D through induction and upregulation of the suppressive activity of regulatory T ( T R e g ) cells. Vitamin D may also promote T R e g cell tropism to dermal sites. In the current study, we examined the capacity of dietary vitamin D 3 to modulate skin inflammation and the numbers and activity of T R e g cells in skin and other sites including lungs, spleen, and blood. In female BALB/c mice, dietary vitamin D 3 suppressed the effector phase of a biphasic ear swelling response induced by dinitrofluorobenzene in comparison vitamin D 3 -deficient female BALB/c mice. Vitamin D 3 increased the percentage of T R e g (CD3+CD4+CD25+Foxp3+) cells in the skin-draining lymph nodes (SDLN). The suppressive activity of T R e g cells in the SDLN, mesenteric lymph nodes, spleen, and blood was upregulated by vitamin D 3 . However, there was no difference in the expression of the naturally occurring T R e g cell marker, neuropilin, nor the expression of CCR4 or CCR10 (skin-tropic chemokine receptors) on T R e g cells in skin, SDLN, lungs, and airway-draining lymph nodes. These data suggest that dietary vitamin D 3 increased the percentages and suppressive activity of T R e g cells in the SDLN, which are poised to suppress dermal inflammation.
Publisher: Frontiers Media SA
Date: 23-03-2021
DOI: 10.3389/FDGTH.2021.626606
Abstract: Despite education about the risks of excessive sun exposure, teenagers in Australia are sun-seeking, with sunburn common in summer. Conversely, some regular (time-limited) exposure to sunlight (that avoids sunburn) is necessary for vitamin D and healthy bones and other molecules important for immune and metabolic health. New interventions are thus required to better support teenagers to make healthy and balanced decisions about their sun behaviors. This paper describes the development of a prototype online tool—a smartphone app—that aimed to foster safe sun practices in teenagers. We recruited young adolescents (aged 12–13 years, n = 24) as “co-researchers” to provide ongoing input into the nature and design of the online tool. This age group was selected, as it is a critical time when young people transition from primary education, where “SunSmart” behaviors are entrenched in Australian schools, to high school, where risky behaviors emerge. Through a series of interviews and workshops, we codesigned an Apple iOS smartphone app with the co-researchers, leading health promotion professionals, researchers, and app designers. The developed app, Sun Safe , contains educational content relevant to teenagers about safe sun behaviors, complemented by other features requested by co-researchers and stakeholders to help engage young people, including gamified quizzes to test their sun health knowledge, real-time weather data on the UV Index and temperature, a sunscreen application timer, and reminders to check the UV Index. The developed prototype app was rated well by co-researchers, suggesting it is suitable for further feasibility and efficacy testing as an intervention tool to improve knowledge and promote safe sun behaviors by young adolescents.
Publisher: American Thoracic Society
Date: 15-05-2011
Publisher: Springer Science and Business Media LLC
Date: 31-07-2018
DOI: 10.1038/S41598-018-29759-Y
Abstract: Vitamin D has been suggested as a possible adjunctive treatment to ameliorate disease severity in human inflammatory bowel disease. In this study, the effects of diets containing high (D++, 10,000 IU/kg), moderate (D+, 2,280 IU/kg) or no vitamin D (D−) on the severity of dextran sodium sulphate (DSS) colitis in female C57Bl/6 mice were investigated. The group on high dose vitamin D (D++) developed the most severe colitis as measured by blinded endoscopic (p 0.001) and histologic (p 0.05) assessment, weight loss (p 0.001), drop in serum albumin (p = 0.05) and increased expression of colonic TNF-α (p 0.05). Microbiota analysis of faecal DNA showed that the microbial composition of D++ control mice was more similar to that of DSS mice. Serum 25(OH)D 3 levels reduced by 63% in the D++ group and 23% in the D+ group after 6 days of DSS treatment. Thus, high dose vitamin D supplementation is associated with a shift to a more inflammatory faecal microbiome and increased susceptibility to colitis, with a fall in circulating vitamin D occurring as a secondary event in response to the inflammatory process.
Publisher: JMIR Publications Inc.
Date: 18-08-2022
DOI: 10.2196/35203
Publisher: Cambridge University Press (CUP)
Date: 04-2005
DOI: 10.1017/S0950268805003717
Abstract: To control plagues of free-living mice (Mus domesticus) in Australia, a recombinant murine cytomegalovirus (MCMV) expressing fertility proteins is being developed as an immunocontraceptive agent. Real-time quantitative PCR was used to monitor the transmission of two genetically variable field strains of MCMV through mouse populations after 25% of founding mice were infected with the N1 strain, followed by the G4 strain 6 weeks later. Pathogen-free wild-derived mice were released into outdoor enclosures located in northwestern Victoria (Australia). Of those mice not originally inoculated with virus, N1 DNA was detected in more than 80% of founder mice and a third of their offspring and similarly, G4 DNA was detected in 13% of founder mice and in 3% of their offspring. Thus, prior immunity to N1 did not prevent transmission of G4. This result is promising for successful transmission of an immunocontraceptive vaccine through Australian mouse populations where MCMV infection is endemic.
Publisher: Wiley
Date: 11-2016
DOI: 10.14814/PHY2.13021
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: The American Association of Immunologists
Date: 06-2013
Abstract: Alterations to dendritic cell (DC) progenitors in the bone marrow (BM) may contribute to long-lasting systemic immunosuppression (& d) following exposure of the skin of mice to erythemal UV radiation (UVR). DCs differentiated in vitro from the BM of mice 3 d after UVR (8 kJ/m2) have a reduced capacity to initiate immunity (both skin and airways) when adoptively transferred into naive mice. Studies in IL-10−/− mice suggested that UV-induced IL-10 was not significantly involved. To investigate the immune capabilities of peripheral tissue DCs generated in vivo from the BM of UV-irradiated mice, chimeric mice were established. Sixteen weeks after reconstitution, contact hypersensitivity responses were significantly reduced in mice reconstituted with BM from UV-irradiated mice (UV-chimeric). When the dorsal skin of UV-chimeric mice was challenged with innate inflammatory agents, the hypertrophy induced in the draining lymph nodes was minimal and significantly less than that measured in control-chimeric mice challenged with the same inflammatory agent. When DCs were differentiated from the BM of UV-chimeric mice using FLT3 ligand or GM-CSF + IL-4, the cells maintained a reduced priming ability. The diminished responses in UV-chimeric mice were not due to different numerical or proportional reconstitution of BM or the hematopoietic cells in blood, lymph nodes, and skin. Erythemal UVR may imprint a long-lasting epigenetic effect on DC progenitors in the BM and alter the function of their terminally differentiated progeny.
Publisher: Springer Science and Business Media LLC
Date: 04-2010
DOI: 10.1039/B9PP00136K
Abstract: Asthma is a chronic inflammatory disease of the small and large conducting airway mucosa characterised by Th2 cell immunity. Allergen-specific IgE levels control the immediate response whilst the interplay between airway mucosal antigen presenting cells, Th2 effector cells and CD4+CD25+ regulatory T cells control the late phase, cell-mediated response. Using two experimental systems in mice with ovalbumin and papain, respectively, as the allergens, UV irradiation of skin prior to allergen sensitisation reduced the expression of allergic airways disease, particularly the late phase response. In this review, the reduced Th2-driven, asthma-like responses in respiratory tissues of UV-irradiated mice are detailed. Possible mechanisms of UV regulation are debated. The potential beneficial effects of UV irradiation of skin in controlling allergic airways disease are discussed. This review gives some scientific understanding to century-old anecdotal reports that beach and mountain resort holidays associated with increased UV exposure are beneficial in asthma treatment.
Publisher: Bioscientifica
Date: 04-2017
DOI: 10.1530/JOE-16-0616
Abstract: Exposure to sunlight may limit cardiometabolic risk. In our previous studies, regular exposure to sub-erythemal (non-burning) ultraviolet radiation (UVR) reduced signs of adiposity and cardiometabolic dysfunction in mice fed a high-fat diet. Some of the observed effects were dependent on skin release of nitric oxide after UVR exposure. Here, we examine the effects of sub-erythemal UVR on signs of adiposity and metabolic dysfunction in already overweight mice, comparing the effects of two sunl s with distinct emitted light spectra. Mice were fed a high-fat diet from 8 weeks of age, with UVR administered twice a week from 14 weeks of age until they were killed at 20 weeks of age. Mice were irradiated with the same dose of UVB radiation (1 kJ/m 2 ) from either FS40 (65% UVB, 35% UVA) or CLEO (4% UVB, 96% UVA) sunl s, but substantially more UVA from the latter. FS40 UVR (but not CLEO UVR) significantly reduced mouse weights and weight gain, compared to mice fed a high-fat diet (only). These effects were dependent on nitric oxide. Conversely, CLEO UVR (but not FS40 UVR) significantly reduced circulating LDL cholesterol. Both light sources reduced fasting insulin levels, and the extent of hepatic steatosis the latter was reversed by topical application of cPTIO, suggesting an important role for skin release of nitric oxide in preventing hepatic lipid accumulation. These results suggest that there may be a number of benefits achieved by regular exposure to safe (non-burning) levels of sunlight or UV-containing phototherapy, with effects potentially dependent on the predominance of the wavelengths of UVR administered.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1038/JID.2010.167
Abstract: Vitamin D may be responsible for reducing the development and severity of autoimmune and allergic diseases. Topically applied 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) enhances the immunoregulatory ability of CD4+CD25+ T cells residing in the skin-draining lymph nodes (SDLNs) of mice. The mechanisms responsible were investigated by examining the expression of 84 cytokine and cytokine-related genes in a 96-well gene array. CD4+CD25+ cells isolated from the SDLNs of BALB/c mice, 24 and 96 hours after topical treatment with 1,25(OH)(2)D(3), consistently expressed increased IL-2 mRNA levels and also secreted enhanced quantities of IL-2 after ex vivo stimulation with phorbol 12-myristate 13-acetate and ionomycin. CD4+CD25+ cells from the lymph nodes of naive mice constitutively express the vitamin D receptor, allowing direct modulation by 1,25(OH)(2)D(3). However, in vitro treatment with 1,25(OH)(2)D(3) did not modify the expression of 84 tested cytokine and cytokine-related mRNAs. It was only in the presence of IL-2 that 1,25(OH)(2)D(3) increased the expression of genes including IL-2 and TLR4. Further, 1,25(OH)(2)D(3) enhanced the ability of IL-2 to stimulate CD4+CD25+ cells to proliferate in vitro and also regulate contact hypersensitivity responses on adoptive transfer into naive mice. Therefore, 1,25(OH)(2)D(3) enabled by IL-2 can directly enhance the regulatory potential of CD4+CD25+ T cells to control immune disease.
Publisher: Springer Science and Business Media LLC
Date: 21-09-2016
Publisher: Oxford University Press (OUP)
Date: 09-2017
Abstract: There is widespread concern about the high prevalence of vitamin D deficiency amid evidence to support that such a state may increase the risk of a wide range of adverse health outcomes. Estimating the prevalence of deficiency, as well as establishing linksto health outcomes, requires the accurate and precise measurement of 25-hydroxyvitamin D [25(OH)D] in serum or plasma. Accurate measurement of 25(OH)D underlies the definitions of vitamin D deficiency, insufficiency, and sufficiency and, thus, prevalence estimates. Imprecise measurement of 25(OH)D in epidemiological research can result in incorrect null findingsof associations with disease. When associations withdisease are found, the inaccuracy of measurement forestalls defining the absolute level of 25(OH)D thatis associated with increased risk. For the clinician,both inaccuracy and imprecision are problematic, because clinical care is most often based on a single measurement to define vitamin D status. New initiatives to develop a standard reference method and the assignment of “true” values to s les provide a solution to these problems. The use of standardized assays in large population studies will allow comparisons to be made between populations and over time that have not previously been possible and will improve our understanding of the role of vitaminD in health and disease.
Publisher: Elsevier BV
Date: 07-2010
DOI: 10.1016/J.JSBMB.2010.02.034
Abstract: Topical creams containing the active form of vitamin D (1,25-dihydroxyvitamin D3 1,25(OH)2D3) or analogues of this compound are currently used with some success to treat skin conditions including psoriasis and vitiligo. As well as targeting inflammatory processes in the skin, topical application of 1,25(OH)2D3 also affects the function of immune cells in the skin and draining lymph nodes. Topically applied 1,25(OH)2D3 reduces the number of dendritic cells in the skin, resulting in suppressed immunity and in particular reduced contact hypersensitivity (CHS) responses. Topical 1,25(OH)2D3 may also promote the migration of dendritic cells from the skin to the draining lymph nodes. Skin application of 1,25(OH)2D3 prevented the inflammatory effects of UVB irradiation on lymph node hypertrophy, when cell numbers were examined 4 days after skin treatment. In contrast, when 1,25(OH)2D3 was applied to UVB irradiated skin, there was no reversal in the suppression of CHS responses caused by UVB irradiation. Instead, 1,25(OH)2D3 had an additive effect with UVB to suppress CHS responses to a greater degree than UVB alone. In these studies, 1,25(OH)2D3 was applied to the treated skin of BALB/c mice immediately following UVB irradiation. Finally, topical 1,25(OH)2D3 also enhanced the number and suppressive activity of CD4+CD25+ regulatory T cells in the lymphatic tissue draining skin.
Publisher: Oxford University Press (OUP)
Date: 09-2017
Abstract: The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D [(25(OH)D] level & nM, is unclear. Intramuscular (IM) injection of a large bolus of vitamin D (≥100 000 IU) is used,but its safety is uncertain. In 10 adults given an IM injection of 600 000IU vitamin D3, we measured at baseline and at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D3,25(OH)D3, 25(OH)D2, total 25(OH)D, 3-epi-25(OH)D3, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] using a standardized LC with tandem MS (MS/MS)assay serum levels of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay and markers of bone metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks. All participants had baseline total 25(OH)D levels & nM. Serum 25(OH)D levels increased at 3, 4, and 24 weeks postinjection, peaking at 4 weeks [mean ± SEM of 126 ± 7.9nM (immunoassay) and 100 ± 5.5 nM (LC-MS/MS)]but generally remained & nM, the upper limit recommended by the U.S. Institute of Medicine. Serum 24,25(OH)2D3 levels increased at 3 and 4 weeks postinjection. Serum ionized calcium levels were higher than baseline at 1, 3, and 4 weeks postinjection but remained within the clinicallynormal range. Other biochemical parameters, including other vitamin D metabolites, plasma alkaline phosphatase, and parathyroid hormone levels, were unchanged. IM injection of a large bolus of vitamin D effectively increases serum 25(OH)D levels without evidence of metabolic abnormality.
Publisher: American Diabetes Association
Date: 13-10-2014
DOI: 10.2337/DB13-1675
Abstract: The role of vitamin D in curtailing the development of obesity and comorbidities such as the metabolic syndrome (MetS) and type 2 diabetes has received much attention recently. However, clinical trials have failed to conclusively demonstrate the benefits of vitamin D supplementation. In most studies, serum 25-hydroxyvitamin D [25(OH)D] decreases with increasing BMI above normal weight. These low 25(OH)D levels may also be a proxy for reduced exposure to sunlight-derived ultraviolet radiation (UVR). Here we investigate whether UVR and/or vitamin D supplementation modifies the development of obesity and type 2 diabetes in a murine model of obesity. Long-term suberythemal and erythemal UVR significantly suppressed weight gain, glucose intolerance, insulin resistance, nonalcoholic fatty liver disease measures and serum levels of fasting insulin, glucose, and cholesterol in C57BL/6 male mice fed a high-fat diet. However, many of the benefits of UVR were not reproduced by vitamin D supplementation. In further mechanistic studies, skin induction of the UVR-induced mediator nitric oxide (NO) reproduced many of the effects of UVR. These studies suggest that UVR (sunlight exposure) may be an effective means of suppressing the development of obesity and MetS, through mechanisms that are independent of vitamin D but dependent on other UVR-induced mediators such as NO.
Publisher: Springer Science and Business Media LLC
Date: 12-2012
DOI: 10.1039/C2PP25108F
Abstract: Ultraviolet radiation (UVR) from sunlight is immunomodulatory and the main source of vitamin D for humans. Vitamin D can also regulate adaptive immunity, through mechanisms that involve the induction or activation of regulatory T cells. Similar mechanisms have also been proposed for the induction of regulatory T cells after skin exposure to UVR. Here we discuss the converging and erging immunoregulatory pathways of UVR and vitamin D, including the molecular pathways for regulatory T cell induction, non-genomic pathways regulated by vitamin D, antimicrobial peptides, skin integrity and potential interactions between vitamin D and other UVR-induced mediators. We then discuss possible in vivo approaches that could be used to demonstrate a direct (or otherwise) role for vitamin D in mediating the immunosuppressive effects of UVR such as the use of dietary vitamin D restriction to induce vitamin D deficiency, gene knockout mice or drugs to block enzymes of vitamin D metabolism. We end with discussion of the epigenetic effects of vitamin D and UVR for immunosuppression.
Publisher: American Physiological Society
Date: 09-2016
DOI: 10.1152/AJPLUNG.00026.2016
Abstract: Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation, and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung s les were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance, and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid droplet-associated, which is associated with ASM remodeling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex.
Publisher: MDPI AG
Date: 05-05-2015
DOI: 10.3390/NU7053219
Publisher: MDPI AG
Date: 18-11-2020
DOI: 10.3390/BIOMEDICINES8110514
Abstract: Recent preclinical data show that sodium glucose cotransporter 2 (SGLT2) inhibitors are able to reduce weight gain and induce beiging in white adipose tissue (WAT). We have previously shown that in neurogenic hypertensive Schlager (BPH/2J) mice, treatment with the SGLT2 inhibitor, Dapagliflozin, reduced blood pressure and prevented weight gain. Here we show that chemical sympathetic denervation achieved by systemic administration of 6-hydroxy-dopamine (6-OHDA) reduces body weight and the heightened sympathetic nervous system (SNS) innervation in WAT. Furthermore, we demonstrate that 2 weeks of Dapagliflozin treatment increases SNS innervation in WAT of hypertensive mice. This increase is accompanied by a non-significant elevation in mRNA levels of the Ucp1 and Pgc-1α genes, which are markers of beiging. No significant difference in the mRNA levels of the inflammatory mediators Il-6 and Tnf-α were detected in WAT of Dapagliflozin treated mice. These findings suggest that SGLT-2 inhibitor-associated prevention of weight gain may be mediated, at least in part, by inducing the beiging of WAT.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2019
DOI: 10.1186/S12931-019-0976-3
Abstract: Epidemiological studies have identified strong relationships between maternal obesity and offspring respiratory dysfunction however, the causal direction is not known. We tested whether maternal obesity alters respiratory function of offspring in early life. Female C57Bl/6 J mice were fed a high or low fat diet prior to and during two rounds of mating and resulting pregnancies with offspring lung function assessed at 2 weeks of age. The lung function of dams was measured at 33 weeks of age. A high fat diet caused significant weight gain prior to conception with dams exhibiting elevated fasting glucose, and glucose intolerance. The number of surviving litters was significantly less for dams fed a high fat diet, and surviving offspring weighed more, were longer and had larger lung volumes than those born to dams fed a low fat diet. The larger lung volumes significantly correlated in a linear fashion with body length. Pups born from the second pregnancy had reduced tissue elastance compared to pups born from the first pregnancy, regardless of the dam’s diet. As there was reduced offspring survival born to dams fed a high fat diet, the statistical power of lung function measures of offspring was limited. There were signs of increased inflammation in the bronchoalveolar lavage fluid of dams (but not offspring) fed a high fat diet, with more tumour necrosis factor-α, interleukin(IL)-5, IL-33 and leptin detected. Dams that were fed a high fat diet and became pregnant twice had reduced fasting glucose immediately prior to the second mating, and lower levels of IL-33 and leptin in bronchoalveolar lavage fluid. While maternal high fat diet compromised litter survival, it also promoted somatic and lung growth (increased lung volume) in the offspring. Further studies are required to examine downstream effects of this enhanced lung volume on respiratory function in disease settings.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2019
DOI: 10.1007/S00125-019-05022-5
Abstract: Exposure to sunlight has the potential to suppress metabolic dysfunction and obesity. We previously demonstrated that regular exposure to low-doses of ultraviolet radiation (UVR) reduced weight gain and signs of diabetes in male mice fed a high-fat diet, in part via release of nitric oxide from skin. Here, we explore further mechanistic pathways through which low-dose UVR exerts these beneficial effects. We fed mice with a luciferase-tagged Ucp1 gene (which encodes uncoupling protein-1 [UCP-1]), referred to here as the Ucp1 luciferase transgenic mouse ('Thermomouse') a high-fat diet and examined the effects of repeated exposure to low-dose UVR on weight gain and development of metabolic dysfunction as well as UCP-1-dependent thermogenesis in interscapular brown adipose tissue (iBAT). Repeated exposure to low-dose UVR suppressed the development of glucose intolerance and hepatic lipid accumulation via dermal release of nitric oxide while also reducing circulating IL-6 (compared with mice fed a high-fat diet only). Dietary nitrate supplementation did not mimic the effects of low-dose UVR. A single low dose of UVR increased UCP-1 expression (by more than twofold) in iBAT of mice fed a low-fat diet, 24 h after exposure. However, in mice fed a high-fat diet, there was no effect of UVR on UCP-1 expression in iBAT (compared with mock-treated mice) when measured at regular intervals over 12 weeks. More extensive circadian studies did not identify any substantial shifts in UCP-1 expression in mice exposed to low-dose UVR, although skin temperature at the interscapular site was reduced in UVR-exposed mice. The appearance of cells with a white adipocyte phenotype ('whitening') in iBAT induced by consuming the high-fat diet was suppressed by exposure to low-dose UVR in a nitric oxide-dependent fashion. Significant shifts in the expression of important core gene regulators of BAT function (Dio2, increased more than twofold), fatty acid transport (increased Fatp2 [also known as Slc27a2]), lipolysis (decreased Atgl [also known as Pnpla2]), lipogenesis (decreased Fasn) and inflammation (decreased Tnf), and proportions of macrophages (increased twofold) were observed in iBAT of mice exposed to low-dose UVR. These effects were independent of nitric oxide released from skin. Our results suggest that non-burning (low-dose) UVR suppresses the BAT 'whitening', steatotic and pro-diabetic effects of consuming a high-fat diet through skin release of nitric oxide, with some metabolic and immune pathways in iBAT regulated by UVR independently of nitric oxide.
Publisher: Wiley
Date: 08-2017
DOI: 10.14814/PHY2.13371
Publisher: Public Library of Science (PLoS)
Date: 24-06-2013
Publisher: Elsevier BV
Date: 06-2023
Publisher: Public Library of Science (PLoS)
Date: 26-09-2012
Publisher: Springer Science and Business Media LLC
Date: 12-2011
DOI: 10.1039/C1PP05206C
Abstract: Exposure of skin to UV radiation (UVR) prior to allergen exposure can inhibit inflammatory airways disease in mice by reducing effector CD4+ T cells in both the trachea and the airway draining lymph nodes. This study analysed the immunomodulatory properties of UVR delivered to naïve versus allergen pre-sensitised mice. In a model of inflammatory airways disease, BALB/c mice were sensitised by peritoneal injection of the allergen, ovalbumin (OVA) (20 μg/mouse), in the adjuvant, alum (4 mg/mouse), on days 0 and 14. On day 21, the mice were exposed to aerosolised OVA and 24 h later, proliferative responses by the cells in the airway draining lymph nodes were examined. UVR (8 kJ m(-2)) was administered 3 days prior to first OVA sensitisation (day -3), or OVA aerosol challenge (day 18). UVR before sensitisation reduced immune responses associated with expression of allergic airways disease seven days after first OVA sensitisation, regulation of OVA-induced proliferation in vitro but not in vivo by CD4+CD25+ cells from UV-irradiated mice was detected. UVR administered to pre-sensitised mice regulated allergen responsiveness by cells from the airway draining lymph nodes only with a sensitisation protocol involving allergen and adjuvant at 5% strength of the original dose (1 μg OVA in 0.2 mg alum/mouse). These results suggest that UVR may modulate allergic airways disease by two mechanisms. The first, and more potent, is by reducing effector cells in respiratory tissues and requires UV delivery prior to sensitisation. The second, associated with administration to pre-sensitised mice, is weaker and is detected when the mice are sensitised with lower levels of allergen and adjuvant.
Publisher: The American Association of Immunologists
Date: 06-2005
DOI: 10.4049/JIMMUNOL.174.11.6677
Abstract: UVB irradiation of the shaved dorsal skin of mice can cause both local and systemic suppression of contact hypersensitivity responses the former demonstrated by administration of the sensitizing Ag/hapten to the irradiated site and the latter by its administration at least 72 h later to distal unirradiated sites. The immunological basis of systemic immunomodulation is not clear. When haptens (trinitrochlorobenzene, FITC) were administered to the shaved ventral skin 4 days after irradiation (8 kJ/m2) to the shaved dorsum of BALB/c mice, CD11c+/FITC+ cells in the skin-draining lymph nodes from control and irradiated mice produced on a per cell basis similar levels of IL-12 and PGE2 were phenotypically mature and efficient at presenting FITC to lymphocytes from FITC-sensitized mice. Ag presentation by FACS-sorted CD11c+ lymph node cells isolated 4 days after UVB irradiation was as efficient as were cells from unirradiated mice at presentation in vitro of an OVA peptide (OVA323–339) to CD4+ cells from OVA-TCR-transgenic DO11.10 mice. Further, IFN-γ levels were increased in the cultures containing CD11c+ cells from UVB-irradiated mice, suggesting that inflammation may precede downstream immunosuppression. These results suggest that the primary cause of reduced contact hypersensitivity responses in mice in which UV irradiation and the sensitizing Ag are applied to different sites several days apart must originate from cells other than CD11c+ APCs that directly or by production of soluble mediators (IL-12, PGE2) affect cellular responses in the nodes of UVB-irradiated mice.
Publisher: Springer Science and Business Media LLC
Date: 02-2018
DOI: 10.1007/S00403-018-1814-Z
Abstract: Topical application of biologically active vitamin D [1,25-dihydroxyvitamin D (1,25(OH)
Publisher: JMIR Publications Inc.
Date: 22-11-2021
Abstract: balanced approach toward sun exposure and protection is needed by young people. Excessive sun exposure increases their risk for skin cancers such as melanoma, whereas some exposure is necessary for vitamin D and healthy bones. We have developed a new iOS smartphone app—Sun Safe—through a co-design process, which aims to support healthy and balanced decision-making by young teenagers (aged 12-13 years). he aim of this study was to test the capacity of Sun Safe to improve sun health knowledge and behaviors of young teenagers in 3 pilot intervention studies completed in 2020. oung teenagers (aged 12-13 years N=57) were recruited through the web or through a local school via an open-access website and given access to Sun Safe (29/57, 51%) or a placebo (SunDial) app (28/57, 49%). Participants completed sun health questionnaires and knowledge quizzes before and after the 6-week intervention (either on the web or in class) and rated the quality of the app they used via a survey. f the 57 participants, 51 (89%) participants (26, 51% for placebo arm and 25, 49% for the Sun Safe arm) completed these studies, with most (& %) reporting that they used a smartphone to access their designated app either “once a fortnight” or “once/twice in total.” Improved sun health knowledge—particularly about the UV Index—was observed in participants who were given access to Sun Safe compared with those who used the placebo (−6.2 [percentage correct] difference in predicted means, 95% CI –12.4 to –0.03 i P /i =.049 2-way ANOVA). Unexpectedly, there were significantly more sunburn events in the Sun Safe group (relative risk 1.7, 95% CI 1.1-1.8 i P /i =.02 Fisher exact test), although no differences in time spent outdoors or sun-protective behaviors were reported. COVID-19 pandemic–related community-wide shutdowns during April 2020 (when schools were closed) reduced the time spent outdoors by & minutes per day (–105 minutes per day difference in predicted means, 95% CI –150 to –59 minutes per day i P /i =.002 paired 2-tailed Student i t /i test). Sun Safe was well-rated by participants, particularly for information (mean 4.2, SD 0.6 out of 5). ccess to the Sun Safe app increased sun health knowledge among young teenagers in these pilot intervention studies. Further investigations with larger s le sizes are required to confirm these observations and further test the effects of Sun Safe on sun-protective behaviors.
Publisher: Springer Science and Business Media LLC
Date: 19-08-2011
DOI: 10.1038/NRI3045
Abstract: Humans obtain most of their vitamin D through the exposure of skin to sunlight. The immunoregulatory properties of vitamin D have been demonstrated in studies showing that vitamin D deficiency is associated with poor immune function and increased disease susceptibility. The benefits of moderate ultraviolet (UV) radiation exposure and the positive latitude gradients observed for some immune-mediated diseases may therefore reflect the activities of UV-induced vitamin D. Alternatively, other mediators that are induced by UV radiation may be more important for UV-mediated immunomodulation. Here, we compare and contrast the effects of UV radiation and vitamin D on immune function in immunopathological diseases, such as psoriasis, multiple sclerosis and asthma, and during infection.
Publisher: Springer Science and Business Media LLC
Date: 10-02-2015
Publisher: MDPI AG
Date: 03-10-2019
Abstract: Seasonality in glucose metabolism has been observed in adult populations however, little is known of the associations between season and glucose metabolism in children. In this study, we examined whether markers of glucose metabolism (fasting glucose, insulin and HbA1c) varied by season in a paediatric population (6–13 years of age) located in Perth (Western Australia, n = 262) with data categorised by weight. Linear regression was used to analyse the nature of the relationships between mean daily levels of terrestrial ultraviolet radiation (UVR) (prior to the day of the blood test) and measures of glucose metabolism. Fasting blood glucose was significantly lower in autumn compared to spring, for children in combined, normal and obese weight categories. Fasting insulin was significantly lower in autumn and summer compared to winter for in iduals of normal weight. HbA1c was significantly higher in summer (compared with winter and spring) in overweight children, which was in the opposite direction to other published findings in adults. In children with obesity, a strong inverse relationship (r = −0.67, p = 0.002) was observed for fasting glucose, and daily terrestrial UVR levels measured in the previous 6 months. Increased safe sun exposure in winter therefore represents a plausible means of reducing fasting blood sugar in children with obesity. However, further studies, using larger paediatric cohorts are required to confirm these relationships.
Publisher: The American Association of Immunologists
Date: 11-2007
DOI: 10.4049/JIMMUNOL.179.9.6273
Abstract: The immunomodulatory effects of vitamin D have been described following chronic oral administration to mice or supplementation of cell cultures with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D. In this study, topically applied 1,25(OH)2D3, enhanced the suppressive capacity of CD4+CD25+ cells from the draining lymph nodes. The effects of topical 1,25(OH)2D3 were compared with those of UVB irradiation, which is the environmental factor required for 1,25(OH)2D3 production in skin. CD4+ cells from the skin-draining lymph nodes (SDLN) of either 1,25(OH)2D3-treated or UVB-irradiated mice had reduced capacity to proliferate to Ags presented in vitro, and could suppress Ag-specific immune responses upon adoptive transfer into naive mice. This regulation was lost upon removal of CD4+CD25+ cells. Furthermore, purified CD4+CD25+ cells from the SDLN of 1,25(OH)2D3-treated or UVB-irradiated mice compared with equal numbers of CD4+CD25+ cells from control mice had increased capacity to suppress immune responses in both in vitro and in vivo assay systems. Following the sensitization of recipient mice with OVA, the proportion of CD4+Foxp3+ cells of donor origin significantly increased in recipients of CD4+CD25+ cells from the SDLN of 1,25(OH)2D3-treated mice, indicating that these regulatory T cells can expand in vivo with antigenic stimulation. These studies suggest that 1,25(OH)2D3 may be an important mediator by which UVB-irradiation exerts some of its immunomodulatory effects.
Publisher: The American Association of Immunologists
Date: 15-12-2010
Abstract: Direct UV irradiation of dendritic cells and Langerhans cells reduces their Ag presenting ability. However, the effects of UV on CD11c+ cells located distally to the point of irradiation are poorly understood. Three days after UV irradiation (8 kJ/m2) of BALB/c mice, bone marrow cells were isolated and cultured for 7 d with IL-4 and GM-CSF for the propagation of CD11c+ cells. Bone marrow-derived CD11c+ cells from UV-irradiated or nonirradiated mice were loaded with dinitrobenzene sulfonic acid and injected into the ear pinnas of naive BALB/c mice. After 7 d, the ears were painted with 2,4-dinitro-1-fluorobenzene and the ear swelling determined 24 h later. A reduced contact hypersensitivity response was found in mice injected with CD11c+ cells from the UV-irradiated animals compared with those injected with cells from the nonirradiated animals. Further, a long-lasting suppression of the memory response to 2,4-dinitro-1-fluorobenzene was created. This suppressed response corresponded to increased IL-10 and PGE2 secretion by freshly isolated bone marrow cells from UV-irradiated mice, and to increased myelopoiesis. The reduction in competence of bone marrow-derived CD11c+ cells from UV-irradiated mice was not due to delayed maturation, as it was maintained upon LPS exposure prior to CD11c+ cell purification. The UV-induced effect was reversed by the administration of indomethacin to mice prior to UV irradiation and could be reproduced by s.c. PGE2. These results show that UV irradiation of mice can affect the function of bone marrow-derived CD11c+ cells via a mechanism inhibitable by indomethacin this pathway is likely to contribute to systemic UV-induced immunosuppression.
Publisher: MDPI AG
Date: 11-10-2016
Publisher: Frontiers Media SA
Date: 03-02-2022
DOI: 10.3389/FNEUR.2022.835162
Abstract: The immunological mechanisms that contribute to multiple sclerosis (MS) differ between males and females. Females are 2–3 times more likely to develop MS compared to males, however the reason for this discrepancy is unknown. Once MS is established, there is a more inflammatory yet milder form of disease in females whereas males generally suffer from more severe disease and faster progression, neural degradation, and disability. Some of these differences relate to genetics, including genetic control of immune regulatory genes on the X-chromosome, as well as immune modulatory properties of sex hormones. Differences in MS development may also relate to how sex interacts with environmental risk factors. There are several environmental risk factors for MS including late-onset Epstein Barr virus infection, low serum vitamin D levels, low UV radiation exposure, smoking, obesity, and lack of physical activity. Most of these risk factors impact males and females differently, either due to biological or immunological processes or through behavioral differences. In this review, we explore these differences further and focus on how the interaction of environmental risk factors with sex hormones may contribute to significantly different prevalence and pathology of MS in males and females.
Publisher: Elsevier BV
Date: 04-2007
Abstract: The mechanisms by which erythemal UVB irradiation modulates systemic immune responses to antigens applied to non-irradiated sites are poorly understood. In this study, regulatory CD4+ T cells were identified in the skin-draining lymph nodes (SDLNs) of UVB-irradiated, but otherwise naive mice. A transgenic mouse strain (DO11.10) was utilized in which the majority of CD4+ T cells expressed the ovalbumin (OVA(323-339)) T-cell receptor. Thus, T-cell responses could be examined following erythemal UVB irradiation without further antigen sensitization. CD4+ T cells from the SDLNs of UVB-irradiated mice had significantly reduced capacity to respond to presentation of the OVA(323-339) peptide in vitro. Transfer of CD4+ T cells from the SDLNs of UVB-irradiated antigen-naive mice significantly reduced both OVA sensitization and contact hypersensitivity responses to an experimental hapten in the recipient mice. Depletion of CD4+CD25+ cells abrogated this UVB-suppressive effect in the in vitro proliferation assay. There was also a significant increase in the proportion of CD4+CD25+Foxp3+ cells in the SDLNs of UVB-irradiated mice. The potential of these regulatory cells poised to regulate responses to incoming antigens at distant non-irradiated sites broadens the biological impact of UVB irradiation of skin on immunity.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.AJPATH.2012.04.007
Abstract: Inflammatory mediators from peripheral tissues may control dendritic cell (DC) development in the bone marrow. In this study, DCs (CD11c(+) cells) differentiated from the bone marrow of mice with inflammation of the airways, or the peritoneal cavity had poor priming ability resulting in reduced, long-lived responses to that antigen in vivo. This indicates enhancement of regulatory mechanisms of immune responses through a peripheral tissue-bone marrow axis. If CD11c(+) cells, expanded from the bone marrow of mice with tissue inflammation were antigen pre-loaded and injected into mice already sensitized to that antigen, then subsequent contact hypersensitivity responses were significantly reduced. The effects of inflammation were imprinted in vivo and were independent of in vitro culture conditions for DC differentiation. The effect of tissue inflammation on the bone marrow DC precursors was not detected in mice treated subcutaneously with slow-release indomethacin pellets, suggesting a role for prostanoids, including prostaglandin E(2), in differentiation of regulatory CD11c(+) cells from bone marrow. Our study represents an important homeostatic process with potential for therapeutic use in the future.
Publisher: Springer Science and Business Media LLC
Date: 03-2017
DOI: 10.1039/C6PP00274A
Abstract: Obesity is increasing in prevalence in many countries around the world. Its causes have been traditionally ascribed to a model where energy intake exceeds energy consumption. Reduced energy output in the form of exercise is associated with less sun exposure as many of these activities occur outdoors. This review explores the potential for ultraviolet radiation (UVR), derived from sun exposure, to affect the development of obesity and two of its metabolic co-morbidities, type-2 diabetes and metabolic syndrome. We here discuss the potential benefits (or otherwise) of exposure to UVR based on evidence from pre-clinical, human epidemiological and clinical studies and explore and compare the potential role of UVR-induced mediators, including vitamin D and nitric oxide. Overall, emerging findings suggest a protective role for UVR and sun exposure in reducing the development of obesity and cardiometabolic dysfunction, but more epidemiological and clinical research is required that focuses on measuring the direct associations and effects of exposure to UVR in humans.
Publisher: Bioscientifica
Date: 03-2020
DOI: 10.1530/JOE-19-0470
Abstract: In previous preclinical studies, low (non-burning) doses of UV radiation (UVR) limited weight gain and metabolic dysfunction in mice fed with a high-fat diet. Here, we explored the effects of low-dose UVR on physical activity and food intake and mechanistic pathways in interscapular brown adipose tissue (iBAT). Young adult C57Bl/6J male mice, housed as in iduals, were fed a high-fat diet and exposed to low-dose UVR (sub-oedemal, 1 kJ/m 2 UVB, twice-a-week) or ‘mock’ treatment, with or without running wheel access (2 h, for ‘moderate’ physical activity) immediately after phototherapy. There was no difference in distance run in mice exposed to UVR or mock-treated over 12 weeks of exposure to running wheels ( P = 0.14). UVR (alone) did not significantly affect food intake, adiposity, or signs of glucose dysfunction. Access to running wheels increased food intake (after 10 weeks, P ≤ 0.02) and reduced gonadal white adipose tissue and iBAT mass ( P ≤ 0.03). Body weight and hepatic steatosis were lowest in mice exposed to UVR with running wheel access. In the iBAT of mice exposed to UVR and running wheels, elevated Atgl , Cd36 , Fasn , Igf1 , Pparγ , and Ucp1 mRNAs and reduced CD11c on F4-80 + MHC class II+ macrophages were observed, while renal Sglt2 mRNA levels were increased, compared to high-fat diet alone ( P ≤ 0.03). Blood levels of 25-hydroxyvitamin D were not increased by exposure to UVR and/or access to running wheels. In conclusion, when combined with physical activity, low-dose UVR may more effectively limit adiposity (specifically, body weight and hepatic steatosis) and modulate metabolic and immune pathways in iBAT.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.JSBMB.2019.105437
Abstract: Accurately detecting vitamin D deficiency (defined as concentration in blood of 25-hydroxyvitamin D (25(OH)D), <20 ng/mL) is important for both clinicians and researchers. Drawing blood may be difficult in some populations, such as infants and children. We thus explored the development of a method to measure 25(OH)D concentrations in saliva, using a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay. Using 25(OH)D
Publisher: Elsevier BV
Date: 04-2014
Publisher: Wiley
Date: 20-05-2021
DOI: 10.1111/IMCB.12460
Abstract: Brown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high-fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPCs)-which give rise to DCs-in bone marrow, with less known of its effects in BAT. We have previously demonstrated that ongoing exposure to low-dose ultraviolet radiation (UVR) significantly reduced the 'whitening' effect of eating a high-fat diet upon interscapular (i) BAT of mice. Here, we examined whether this observation may be linked to changes in the phenotype of HSPCs and myeloid-derived immune cells in iBAT and bone marrow of mice using 12-colour flow cytometry. Many HSPC subsets declined in both iBAT and bone marrow with increasing metabolic dysfunction. Conversely, with rising adiposity and metabolic dysfunction, conventional DCs (cDCs) increased in both of these tissues. When compared with a low-fat diet, consumption of a high-fat diet significantly reduced proportions of myeloid, common myeloid and megakaryocyte-erythrocyte progenitors in iBAT, and short-term hematopoietic stem cells in bone marrow. In mice fed the high-fat diet, exposure to low-dose UVR significantly reduced proportions of cDCs in iBAT, independently of nitric oxide release from irradiated skin [blocked using the scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO)], but did not significantly modify HSPC subsets in either tissue. Further studies are needed to determine whether changes in these cell populations contribute towards metabolic dysfunction .
Publisher: Wiley
Date: 26-07-2007
DOI: 10.1111/J.1365-2222.2007.02750.X
Abstract: Over recent decades, there has been a significant global increase in the prevalence of asthma, an inflammatory disease of the respiratory system. While ultraviolet radiation (UV) has been used successfully in the treatment of inflammatory conditions such as psoriasis, studies of UV-induced regulation of allergic respiratory responses have been rare, and have not analysed in vivo measurements of airway hyperresponsiveness (AHR) or the antigen specificity of the UV-induced effects. To investigate the regulatory properties of erythemal ultraviolet B (UVB) irradiation of the skin and the induction of allergen-induced airway immunity in a murine asthma model, and to examine the mechanisms involved. BALB/c mice were exposed to a single erythemal dose of UV 3 days before intraperitonial sensitization (day 0) and boost (day 14) with the antigen, ovalbumin (OVA). Airway-associated, asthma-like responses to aerosolized OVA at day 21 were analysed including (a) AHR measured in vivo, (b) OVA-specific proliferative responses and cytokine production by cells from the lung-draining lymph nodes (LDLN), and (c) inflammatory cells and cytokines in the bronchoalveolar lavage fluid. To determine UVB-induced mechanisms of regulation, LDLN cells from UVB irradiated, OVA-sensitized mice were adoptively transferred into naïve BALB/c mice that were subsequently sensitized and challenged with OVA, or a non-specific antigen. UVB irradiation of skin significantly suppressed AHR to methacholine and OVA-specific responses in the LDLN and in the lung compartment. Reduced OVA-specific responses by LDLN cells from both UVB irradiated mice and mice that received 5 x 10(6) LDLN cells from UVB irradiated, but not from non-irradiated, OVA-sensitized mice suggested that UVB-induced regulatory cells are responsible for many of the asthma-reducing effects of dorsal UVB exposure. UVB irradiation of skin suppresses AHR and cellular responses of the airways to respiratory allergens. Further, this study implicates UVB or its downstream mediators as a potential approach to reducing the severity of asthma.
Publisher: Oxford University Press (OUP)
Date: 27-08-2013
DOI: 10.1189/JLB.0513294
Abstract: Dendritic cells (DCs) that differentiate in vitro from the bone marrow (BM) of mice with prostaglandin E2 (PGE2)-associated inflammation of the skin, airways, or peritoneal cavity poorly initiate immune responses. To remove in vitro differentiation and allow BM-derived DCs to seed the periphery under steady-state conditions, as well as study the molecule proposed responsible, chimeric mice were engrafted for & wk with BM cells from mice exposed to PGE2. Serial PGE2-chimeric mice were established with BM cells from the primary chimeric mice. Immune responses in the airways and skin of the PGE2-chimeric mice and serial PGE2-chimeric mice were significantly attenuated. After inflammatory challenges by intranasal LPS, topical fluorescein isothiocyanate, and intraperitoneal alum, DCs, macrophages, and neutrophils trafficked poorly in PGE2-chimeric mice and serial PGE2-chimeric mice. Injection of BM-differentiated DCs from nonchimeric mice restored the reduced immune responses of PGE2-chimeric mice. DCs from BM of 16-wk-engrafted PGE2-chimeric and serial PGE2-chimeric mice resembled cells differentiated from BM exposed to PGE2 for only 3 d, demonstrating the long-lasting effect of PGE2 on DC progenitors. PGE2 attenuates systemic immune responses by modulating myeloid cell progenitors in the BM such that BM-derived, terminally differentiated myeloid cells have poor trafficking ability to sites of need.
Publisher: Elsevier BV
Date: 09-2020
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000517642
Abstract: While UV radiation is a skin carcinogen, this should not obscure the growing evidence that sunlight has significant health benefits, including impacts on cardiovascular and metabolic health. Epidemiological and mechanistic evidences for the importance of different wavelengths of sunlight, including blue light and UV radiation, are presented.
Publisher: Proceedings of the National Academy of Sciences
Date: 19-01-2022
Abstract: Spillover of infectious diseases from wildlife populations into humans is an increasing threat to human health and welfare. Current approaches to manage these emerging infectious diseases are largely reactive, leading to deadly and costly time lags between emergence and control. Here, we use mathematical models and data from previously published experimental and field studies to evaluate the scope for a more proactive approach based on transmissible vaccines that eliminates pathogens from wild animal populations before spillover can occur. Our models are focused on transmissible vaccines designed using herpes virus vectors and demonstrate that these vaccines—currently under development for several important human pathogens—may have the potential to rapidly control zoonotic pathogens within the reservoir hosts.
Publisher: Springer Science and Business Media LLC
Date: 23-03-2013
Publisher: Elsevier BV
Date: 07-2008
DOI: 10.1016/J.VACCINE.2008.05.020
Abstract: We have developed a murine cytomegalovirus (MCMV)-vectored vaccine expressing the mouse zona-pellucida-3 gene (rMCMV-ZP3), which successfully induces infertility in experimentally inoculated laboratory or wild-derived mice. However, the future success of this vector as a fully disseminating vaccine in free-living mice may be compromised by pre-existing immunity since there is a high prevalence of naturally acquired MCMV infection in these mice. To evaluate the effect of prior immunity to MCMV on vaccine efficacy, we constructed two new biologically effective recombinant MCMV vectors expressing the mouse ZP3 protein from two MCMV strains (N1 and G4) derived from free-living mice. In wild mice, mixed MCMV infection is common and could be acquired either by simultaneous coinfection or sequential infection with different MCMV strains. Interestingly, while coinfection with both wild-type and rMCMV-ZP3 via the intraperitoneal route reduced the impact of the rMCMV-ZP3, prior infection with the same wild-type strain as that used to construct the rMCMV-ZP3 abrogated the immunocontraceptive effects of either N1-ZP3 or G4-ZP3. However, prior infection with G4 28 days before the introduction of N1-ZP3 had a reduced influence on the efficacy of the rMCMV-ZP3. Thus, the strain of virus and the timing of prior infection are factors that may influence the efficacy of the rMCMV-ZP3. Given that mixed infection of mice with MCMV is common, it is possible that prior immunity acquired by natural mucosal infection may have less a less inhibitory effect on the immunocontraceptive outcome.
Start Date: 2018
End Date: 03-2019
Amount: $621,198.00
Funder: Australian Research Council
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