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


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
Publication statusPublished - 24 Nov 2020


  • vitamin D
  • multiple sclerosis
  • type I regulatory T cells
  • adhesion
  • CD46
  • CD226
  • RISK
  • EAE

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