Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity.
Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity.
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DOI：
10.1038/s41590-021-00948-8
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发表时间：
2021-07
影响因子：
30.5
通讯作者：
Korn T
中科院分区：
文献类型：
--
作者：
Hiltensperger M;Beltrán E;Kant R;Tyystjärvi S;Lepennetier G;Domínguez Moreno H;Bauer IJ;Grassmann S;Jarosch S;Schober K;Buchholz VR;Kenet S;Gasperi C;Öllinger R;Rad R;Muschaweckh A;Sie C;Aly L;Knier B;Garg G;Afzali AM;Gerdes LA;Kümpfel T;Franzenburg S;Kawakami N;Hemmer B;Busch DH;Misgeld T;Dornmair K;Korn T
T细胞的多维单细胞分析引发了关于体内T辅助细胞亚群的广泛可塑性或“混合”引发的争论。在这里，我们开发了一个实验框架，以探讨的想法，在全身免疫室的网站启动是一个决定性的T辅助细胞诱导的免疫病理学在远程器官。通过对腹股沟（i）或肠引流肠系膜（m）淋巴结中抗原特异性T细胞的位点特异性体内标记，我们表明在多发性硬化模型中从发炎的中枢神经系统分离的i-T细胞和m-T细胞是不同的。i-T细胞是Cxcr 6+，m-T细胞表达P2 rx 7。值得注意的是，m-T细胞浸润白色物质，而i-T细胞也被募集到灰质。因此，我们建议，T辅助细胞亚群的定义，其网站的启动可能会引导一个先进的理解T辅助细胞生物学在健康和疾病。
Multidimensional single cell-analyses of T cells have fueled the debate about either extensive plasticity or “mixed” priming of T helper cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of T helper cell-induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system in a model of multiple sclerosis are distinct. i-T cells were Cxcr6+ and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter while i-T cells were also recruited to grey matter. Therefore, we propose that the definition of T helper cell subsets by their site of priming might guide an advanced understanding of T helper cell biology in health and disease.
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