Disrupting Myelin-Specific Th17 Cell Gut Homing Confers Protection in an Adoptive Transfer Experimental Autoimmune Encephalomyelitis
Disrupting Myelin-Specific Th17 Cell Gut Homing Confers Protection in an Adoptive Transfer Experimental Autoimmune Encephalomyelitis
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DOI：
10.1016/j.celrep.2019.09.002
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发表时间：
2019-10-08
期刊：
影响因子：
8.8
通讯作者：
Pot, Caroline
中科院分区：
文献类型：
--
作者：
Duc, Donovan;Vigne, Solenne;Pot, Caroline
多发性硬化（MS）是一种常见的中枢神经系统自身免疫性疾病。虽然观察到MS和炎症性肠病之间的关联，但肠道免疫反应和神经炎症之间的联系仍不清楚。在这里，我们表明，致脑炎性Th 17细胞浸润结肠固有层神经系统症状的发展之前，在两个小鼠MS模型，主动和过继转移实验性自身免疫性脑脊髓炎（EAE）。通过阻断α 4 b7-整联蛋白及其配体MAdCAM-1途径特异性靶向Th 17细胞肠道归巢，削弱了T细胞向大肠的迁移，并减轻了Th 17细胞过继转移模型中EAE的严重程度。从机制上讲，髓鞘特异性Th 17细胞在结肠中增殖并影响肠道微生物群组成。阻断α 4 b7-整联蛋白及其配体MAdCAM-1通路对EAE的有益作用与肠道微生物群相互依赖。这些结果表明，破坏髓鞘特异性Th 17细胞向大肠的运输利用了神经炎症，并表明肠道环境和微生物群催化了Th 17细胞的致脑炎特性。
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.