期刊
CELL REPORTS
卷 29, 期 2, 页码 378-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.09.002
关键词
-
类别
资金
- Swiss National Science Foundation [323630-183987, PP00P3_157476]
- Leenaards Foundation
- Swiss National Science Foundation (SNF) [PP00P3_157476] Funding Source: Swiss National Science Foundation (SNF)
Multiple sclerosis (MS) is acommon autoimmune disease of the CNS. Although 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, active and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Specifically targeting Th17 cell intestinal homing by blocking the alpha 4b7-integrin and its ligand MAdCAM-1 pathway impairs T cell migration to the large intestine and dampens EAE severity in the Th17 cell adoptive transfer model. Mechanistically, myelin-specific Th17 cells proliferate in the colon and affect gutmicrobiota composition. The beneficial effect of blocking the alpha 4b7-integrin and its ligandMAdCAM-1 pathway on EAE is interdependent with gut microbiota. Those results show that disrupting myelin-specific Th17 cell trafficking to the large intestine harnesses neuroinflammation and suggests that the gut environment and microbiota catalyze the encephalitogenic properties of Th17 cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据