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Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity.

Nat Immunol. 2021 Jun 7. doi: 10.1038/s41590-021-00948-8. Epub ahead of print. PMID: 34099917.

Authors/Editors: 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.
Publication Date: 2021

Abstract

Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or ‘mixed’ priming of helper T 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 helper T 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 (CNS) in a model of multiple sclerosis (MS) 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 gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease.

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