Science子刊:IL-17通过肠道菌群调控中枢神经系统自身免疫疾病
创作:szx 审核:szx 03月01日
  • IL-17-/-小鼠(同时缺失IL-17A及IL-17F)对EAE的易感性降低;
  • 与IL-17+/-小鼠相比,IL-17-/-小鼠的肠道菌群组成发生显著改变,13个OTU的丰度增加;
  • 将野生型小鼠与IL-17-/-小鼠同窝饲养,可恢复后者的肠道菌群组成及对EAE的易感性;
  • 但将IL-17-/-小鼠的粪菌移植给野生型小鼠,却无法降低后者对EAE的易感性;
  • 缺失IL-17A及IL-17F的Th细胞仍具有致脑炎能力,而肠道上皮的IL-17A表达可恢复IL-17-/-小鼠对EAE的易感性。
主编推荐语
szx
产生IL-17A及IL-17F的Th17细胞在中枢神经系统自身免疫疾病(如多发性硬化)的发展中起重要作用。Science Immunology上发表的一项最新研究,发现IL-17缺失小鼠对实验性自身免疫性脑脊髓炎(EAE)的易感性降低,这一表型与肠道菌群组成的变化相关,而恢复菌群可恢复其对EAE的易感性。进一步研究发现,缺失IL-17的Th细胞并未失去致病性,而在肠道上皮中恢复IL-17A的表达即可恢复IL-17缺失小鼠对EAE的易感性。该研究结果提示,IL-17并非直接介导了EAE,而是通过影响肠道稳态而间接介导了中枢神经系统自身免疫疾病。
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
图片
Science Immunology [IF:13.44]

IL-17 controls central nervous system autoimmunity through the intestinal microbiome

IL-17通过肠道菌群控制中枢神经系统自身免疫

10.1126/sciimmunol.aaz6563

02-05, Article

Abstract & Authors:展开

Abstract:收起
Interleukin-17A– (IL-17A) and IL-17F–producing CD4+ T helper cells (TH17 cells) are implicated in the development of chronic inflammatory diseases, such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). TH17 cells also orchestrate leukocyte invasion of the central nervous system (CNS) and subsequent tissue damage. However, the role of IL-17A and IL-17F as effector cytokines is still confused with the encephalitogenic function of the cells that produce these cytokines, namely, TH17 cells, fueling a long-standing debate in the neuroimmunology field. Here, we demonstrated that mice deficient for IL-17A/F lose their susceptibility to EAE, which correlated with an altered composition of their gut microbiota. However, loss of IL-17A/F in TH cells did not diminish their encephalitogenic capacity. Reconstitution of a wild-type–like intestinal microbiota or reintroduction of IL-17A specifically into the gut epithelium of IL-17A/F–deficient mice reestablished their susceptibility to EAE. Thus, our data demonstrated that IL-17A and IL-17F are not encephalitogenic mediators but rather modulators of intestinal homeostasis that indirectly alter CNS-directed autoimmunity.

First Authors:
Tommy Regen

Correspondence Authors:
Ari Waisman

All Authors:
Tommy Regen,Sandrine Isaac,Ana Amorim,Nicolás Gonzalo Núñez,Judith Hauptmann,Arthi Shanmugavadivu,Matthias Klein,Roman Sankowski,Ilgiz A Mufazalov,Nir Yogev,Jula Huppert,Florian Wanke,Michael Witting,Alexandra Grill,Eric J C Gálvez,Alexei Nikolaev,Michaela Blanfeld,Immo Prinz,Philippe Schmitt-Kopplin,Till Strowig,Christoph Reinhardt,Marco Prinz,Tobias Bopp,Burkhard Becher,Carles Ubeda,Ari Waisman

评论