ORCID Profile
0000-0001-8180-9730
Current Organisation
Washington University in Saint Louis
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 06-2018
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.CYTO.2018.12.024
Abstract: Homozygous mutations in Triggering Receptor Expressed on Myeloid cells 2 gene (TREM2) are one of the major causes of Nasu Hakola Disease (NHD). We analysed Peripheral Blood Mononuclear Cells (PBMC) profile of 164 inflammatory factors in patients with NHD carrying the TREM2 Q33X mutation as compared with heterozygous and wild type in iduals. Several molecules related to bone formation and angiogenesis were altered in NHD compared to non-carriers: Bone Morphogenetic Protein (BMP)-1 mRNA levels were significantly increased in PBMC (2.32 fold-increase P = 0.01), as were Transforming Growth Factor Beta (TGFB)3 levels (1.51 fold-increase P = 0.02). Conversely, CXCL5 and Pro Platelet Basic Protein (PPBP) were strongly downregulated (-28.26, -9.85 fold-decrease over non-carriers, respectively, P = 0.01), as well as Platelet Factor 4 Variant 1 (PF4V1 -41.44, P = 0.03). Among other inflammatory factors evaluated, Interleukin (IL)-15 and Tumor Necrosis Factor Superfamily Member (TNFSF)4 mRNA levels were decreased in NHD as compared with non-carriers (-2.25 and -3.87 fold-decrease, P = 0.01 and 0.001, respectively). In heterozygous in iduals, no significant differences were observed, apart from IL-15 mRNA levels, that were decreased at the same extent as NHD (-2.05 fold-decrease over non-carriers, P = 0.002). We identified a signature in PBMC from patients with NHD consisting of strongly decreased mRNA levels of CXCL5, PPBP, PF4V1, mildly decreased IL-15 and TNFSF4 and mildly increased BMP-1 and TGFB3.
Publisher: SAGE Publications
Date: 25-06-2019
Abstract: Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune demyelinating disease. Its pathogenesis involves humoral and cellular immunity, with production of pro- and anti-inflammatory cytokines by T cells. To analyze the cytokine profile of cerebrospinal fluid (CSF) T cells in patients with relapsing-remitting MS (RRMS) and non-inflammatory controls. T cell cytokine production was analyzed by flow cytometry in CSF s les collected from 34 untreated RRMS patients and 20 age-matched controls. Immunofluorescence studies were performed in spinal cord MS active lesions. Percentages of CSF-derived IL-17A, IL-17A/IL-22, and IL-17A/GM-CSF producing T cells were significantly higher in RRMS patients compared to controls. Percentages of T cells producing IFN-γ were lower in RRMS patients compared to controls. Patients in relapse showed higher percentages of CD4 + T cells producing IL-13 and GM-CSF compared to patients in remission. We found a positive correlation between percentages of IL-13 + T cells and the Expanded Disability Status Scale (EDSS ρ = 0.5 p 0.05). Meningeal IL-13-producing T cells were detected in spinal cord MS active lesions. We observed differences in IL-17, IL-22, and IFN-γ production by CSF T cells in RRMS versus controls and a positive correlation between IL-13-producing T cells and EDSS in RRMS patients.
Publisher: Springer Science and Business Media LLC
Date: 04-10-2016
Publisher: American Society for Clinical Investigation
Date: 07-2021
DOI: 10.1172/JCI143774
Publisher: Rockefeller University Press
Date: 08-01-2021
DOI: 10.1084/JEM.20190086
Abstract: Recent and accumulating work in experimental animal models and humans shows that diet has a much more pervasive and prominent role than previously thought in modulating neuroinflammatory and neurodegenerative mechanisms leading to some of the most common chronic central nervous system (CNS) diseases. Chronic or intermittent food restriction has profound effects in shaping brain and peripheral metabolism, immunity, and gut microbiome biology. Interactions among calorie intake, meal frequency, diet quality, and the gut microbiome modulate specific metabolic and molecular pathways that regulate cellular, tissue, and organ homeostasis as well as inflammation during normal brain aging and CNS neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others. This review discusses these findings and their potential application to the prevention and treatment of CNS neuroinflammatory diseases and the promotion of healthy brain aging.
Publisher: SAGE Publications
Date: 12-10-2015
Abstract: Dimethyl fumarate (DMF) alters the phenotype of circulating immune cells and causes lymphopenia in a subpopulation of treated multiple sclerosis (MS) patients. To phenotypically characterize circulating leukocytes in DMF-treated MS patients. Cross-sectional observational comparisons of peripheral blood from DMF-treated MS patients ( n = 17 lymphopenic and n = 24 non-lymphopenic), untreated MS patients ( n = 17) and healthy controls ( n = 23) immunophenotyped using flow cytometry. Longitudinal s les were analyzed for 13 DMF-treated patients. Lymphopenic DMF-treated patients had significantly fewer circulating CD8 + and CD4 + T cells, CD56 dim natural killer (NK) cells, CD19 + B cells and plasmacytoid dendritic cells when compared to controls. CXCR3 + and CCR6 + expression was disproportionately reduced among CD4 + T cells, while the proportion of T-regulatory (T-reg) cells was unchanged. DMF did not affect circulating CD56 hi NKcells, monocytes or myeloid dendritic cells. Whether lymphopenic or not, DMF-treated patients had a lower proportion of circulating central and effector memory T cells and concomitant expansion of naïve T cells compared to the controls. DMF shifts the immunophenotypes of circulating T cells, causing a reduction of memory cells and a relative expansion of naïve cells, regardless of the absolute lymphocyte count. This may represent one mechanism of action of the drug. Lymphopenic patients had a disproportionate loss of CD8 + T-cells, which may affect their immunocompetence.
Location: Italy
Location: United States of America
No related grants have been discovered for Laura Ghezzi.