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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Calcitriol modulates the CD46 pathway in T cells
Karoline Kickler1, Siobhan Ni Choileain, Anna Williams
1MRC Centre for Inflammation Research, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
Plos One
|November 13, 2012
Summary
Active vitamin D (calcitriol) enhances regulatory T cell responses in multiple sclerosis (MS) by modulating the CD46 pathway. Calcitriol promotes IL-10 secretion, suggesting potential therapeutic benefits for MS patients.
Area of Science:
- Immunology
- Neuroimmunology
- Endocrinology
Background:
- CD46 is a complement regulator and costimulatory molecule for human T cells, inducing a regulatory Tr1 phenotype with high IL-10 secretion.
- IL-10 secretion upon CD46 costimulation is impaired in T cells from multiple sclerosis (MS) patients.
- Vitamin D has direct effects on T cells and may benefit MS pathology.
Purpose of the Study:
- To investigate if active vitamin D (calcitriol) can modulate the CD46 pathway.
- To determine if calcitriol can restore IL-10 production in CD46-costimulated CD4+ T cells from MS patients.
Main Methods:
- Pilot study involving CD4+ T cells from healthy donors and MS patients.
- Analysis of T cell phenotype (CD28, CD25, CTLA-4, Foxp3, CD46 expression) following CD46 costimulation with and without calcitriol.
- Measurement of IL-10 and IFNγ cytokine production to assess the IL-10:IFNγ ratio.
Main Results:
- In healthy T cells, calcitriol increased CD28, CD25, CTLA-4, and Foxp3 expression while decreasing CD46 expression.
- In MS T cells, calcitriol increased CD28, CTLA-4, and Foxp3 but inhibited CD25 induction, unlike in healthy cells.
- Despite aberrant CD25 effects in MS, calcitriol significantly increased the IL-10:IFNγ ratio in both healthy and MS T cells, indicative of a Tr1 phenotype.
Conclusions:
- Calcitriol modulates the CD46 pathway in human T cells.
- Calcitriol promotes anti-inflammatory responses mediated by CD46, including increased IL-10 production.
- Calcitriol shows potential as a therapeutic agent to improve T cell responses in multiple sclerosis.
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