Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis

Justin Killick, Joanne Hay, Elena Morandi, Sonja Vermeren, Saniya Kari, Thibault Angles, Anna Williams, Jan Damoiseaux, Anne L. Astier*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), in which T-cell migration into the CNS is key for pathogenesis. Patients with MS exhibit impaired regulatory T cell populations, and both Foxp3+ Tregs and type I regulatory T cells (Tr1) are dysfunctional. MS is a multifactorial disease and vitamin D deficiency is associated with disease. Herein, we examined the impact of 1,25(OH)2D3 on CD4+ T cells coactivated by either CD28 to induce polyclonal activation or by the complement regulator CD46 to promote Tr1 differentiation. Addition of 1,25(OH)2D3 led to a differential expression of adhesion molecules on CD28- and CD46-costimulated T cells isolated from both healthy donors or from patients with MS. 1,25(OH)2D3 favored Tr1 motility though a Vitamin D-CD46 crosstalk highlighted by increased VDR expression as well as increased CYP24A1 and miR-9 in CD46-costimulated T cells. Furthermore, analysis of CD46 expression on T cells from a cohort of patients with MS supplemented by vitamin D showed a negative correlation with the levels of circulating vitamin D. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis allowed the visualization and identification of clusters increased by vitamin D supplementation, but not by placebo, that exhibited similar adhesion phenotype to what was observed in vitro. Overall, our data show a crosstalk between vitamin D and CD46 that allows a preferential effect of Vitamin D on Tr1 cells, providing novel key insights into the role of an important modifiable environmental factor in MS.

Original languageEnglish
Article number598727
Number of pages16
JournalFrontiers in Immunology
Volume11
DOIs
Publication statusPublished - 24 Nov 2020

Keywords

  • vitamin D
  • multiple sclerosis
  • type I regulatory T cells
  • adhesion
  • CD46
  • 1,25-DIHYDROXYVITAMIN D-3
  • ACTIVATION
  • INDUCTION
  • CYTOKINES
  • CD226
  • RISK
  • EAE

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