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

ABSTRACT: 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 for Multiple Sclerosis are distinct.

ORGANISM(S): Mus musculus

PROVIDER: GSE172513 | GEO | 2021/04/22

REPOSITORIES: GEO

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Skin and gut imprinted T helper cell subsets exhibit distinct functional phenotypes in CNS autoimmunity

Project description: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 for Multiple Sclerosis are distinct.

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

Project description: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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Neonatally imprinted mesenteric lymph node stromal cell subsets induce tolerogenic dendritic cells [endogenous FSCs]

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