Role of vitamin D in T cell migration - Anne Astier - project start: 2017


Vitamin D has known immunomodulatory unctions and vitamin D deficiency has been linked to several chronic inflammatory diseases such as multiple scleroses. Migration of activated T cells to the site of inflammation is crucial for pathogenesis. In MS, the interns VLA44 and LFA41 are key to this process. The team have shown that the bioactive form of vitamin D decreased expression and activation of VLA44, and strongly modulated the pattern of adhesion molecules expressed by activated T cells. Vitamin D similarly affected CD4+ T cells isolated from healthy controls and patients with MS. However, vitamin D promoted T cell chemotaxis, especially of CD464 Costimulated regulatory type I cell ( TR1) compared to CD284 costimulated effector T cell. Phototherapy treatment of patients with atopic dermatitis les to an increased level of circulating vitamin D and a decrease in VLA44 expression on circulating T cells but not on conventional FOXP3+ regulatory T cells (TREGS), suggesting a differential affect of vitamin D on integrin expression in vivo on effector and regulatory T cells. Overall, datas suggest that vitamin D regulates key proteins involved in the control of T cell migration, and that it favors migration of regulatory  cells over effector cells, providing novel insights into the mechanisms of the immunoregulatory role of vitamin D.

The objectivists is to correlate levels of circulating vitamin D with the phenotype of activated purified T cells in vitro in A cohort of healthy donors and untreated patients with RRMS, and assess their migratory abilities in an in vitro BBB MODEL.  

They expect donors with high levels of vitamin D to have enhanced regulatory T cells with migratory abilities coinciding with reduced migration of their effector T cells.