ORCID Profile
0000-0002-9726-0241
Current Organisation
University of South Australia
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Publisher: Springer Science and Business Media LLC
Date: 31-08-2022
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 28-03-2022
DOI: 10.1111/IMM.13472
Abstract: In CD4 + T helper cells, the active form of vitamin D 3 , 1,25‐dihydroxyvitamin D 3 (1,25D) suppresses production of inflammatory cytokines, including interferon‐gamma (IFN‐γ), but the mechanisms for this are not yet fully defined. In innate immune cells, response to 1,25D has been linked to metabolic reprogramming. It is unclear whether 1,25D has similar effects on CD4 + T cells, although it is known that antigen stimulation of these cells promotes an anabolic metabolic phenotype, characterized by high rates of aerobic glycolysis to support clonal expansion and effector cytokine expression. Here, we performed in‐depth analysis of metabolic capacity and pathway usage, employing extracellular flux and stable isotope‐based tracing approaches, in CD4 + T cells treated with 1,25D. We report that 1,25D significantly decreases rates of aerobic glycolysis in activated CD4 + T cells, whilst exerting a lesser effect on mitochondrial glucose oxidation. This is associated with transcriptional repression of Myc, but not repression of mTOR activity under these conditions. Consistent with the modest effect of 1,25D on mitochondrial activity, it also did not impact CD4 + T‐cell mitochondrial mass or membrane potential. Finally, we demonstrate that inhibition of aerobic glycolysis by 1,25D substantially contributes to its immune‐regulatory capacity in CD4 + T cells, since the suppression of IFN‐γ expression was significantly blunted in the absence of aerobic glycolysis. 1,25‐Dihydroxyvitamin D 3 (1,25D) suppresses the production of inflammatory cytokines such as interferon‐gamma (IFN‐γ) by CD4 + T cells, but the underpinning mechanisms are not yet fully defined. Here, we identify that 1,25D inhibits aerobic glycolysis in activated CD4 + T cells, associated with decreased c‐Myc expression. This mechanism appears to substantially contribute to the suppression of IFN‐γ by 1,25D, since this is significantly blunted in the absence of aerobic glycolysis.
Publisher: American Society of Civil Engineers (ASCE)
Date: 09-2020
Publisher: American Society of Civil Engineers (ASCE)
Date: 12-2022
Publisher: Springer Nature Singapore
Date: 28-10-2021
Publisher: Springer Singapore
Date: 11-10-2020
Publisher: Hindawi Limited
Date: 31-03-2019
DOI: 10.1155/2019/8505021
Abstract: Objective . This study is aimed at investigating the association of exhausted CD8 + tumor-infiltrating lymphocytes with clinic-pathological factors. Methods . 133 patients diagnosed with primary invasive ductal breast cancer were recruited into the cross-sectional study consecutively. Immunohistochemistry was used to detect biomarker expression on formalin-fixed and paraffin-embedded sections. Double staining of CD8 and PD-1 was conducted on lymphocytes. Results . The proportion of CD8 + /PD-1 - TILs was 16% among patients with axillary lymph node metastasis, significantly lower than those without metastasis (24%). The expression of CK7, CK20, or Ki-67 was not related with the proportion of phenotypes of CD8/PD-1 TILs. Younger patients had more cell counts of CD8 + /PD-1 - TILs than elderly patients (18/HPF vs. 9/HPF, p 0.05 ). Patients with axillary lymph node metastasis had less CD8 + /PD-1 - TILs than those without metastasis (11/HPF vs. 27/HPF, p 0.05 ). Median counts of CD8 + /PD-1 - TILs among patients with CK20 and E-Cad expression were 33/HPF and 14/HPF, significantly higher than those among patients with negative CK20 (16/HPF) and E-Cad expression (6/HPF). Ki-67 index had a significant correlation with cell counts of CD8 + /PD-1 + TILs and CD8 + /PD-1 - TILs, and the correlation coefficients were 0.19 and 0.21 ( p 0.05 ), respectively. Conclusion . The proportion of CD8 + /PD-1 - TILs was related with metastatic status of the axillary lymph node but cell counts of CD8 + /PD-1 - TILs were related with metastatic status of the axillary lymph node and expression of CK7, CK20, E-Cad, and Ki-67. Absolute cell counts, not proportion of CD8/PD-1 TILs, were more likely to distinguish clinic and pathologic characteristics of breast cancer.
No related grants have been discovered for Tri Le.