BioProject

Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system. More...

Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system. While an association between MS and inflammatory bowel diseases is observed, the link connecting intestinal immune responses and neuroinflammation remains unclear. Here we show that encephalitogenic Th17 cells infiltrate the colonic lamina propria before neurological symptom development in two murine MS models, the active and adoptive-transfer experimental autoimmune encephalomyelitis (EAE). Specifically targeting Th17 intestinal homing by blocking integrin a4b7-MAdCAM-1 pathway impairs T cell migration to the large intestine and dampens EAE severity in Th17 adoptive-transfer model. Mechanistically, myelin-specific Th17 cells proliferate in the colon and affect gut microbiota composition. The beneficial effect of blocking the integrin a4b7-MAdCAM-1 pathway on EAE is interdependent of gut microbiota. Those results show that disrupting myelin-specific Th17 cell trafficking to the large intestine harness neuroinflammation and suggests that the gut environment and microbiota catalyze the encephalitogenic properties of Th17 cell. Less...