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

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

PROVIDER: PRJNA723595 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14295722.fastq.gz	Fastqsanger.gz
	SRR14295723.fastq.gz	Fastqsanger.gz
	SRR14295724.fastq.gz	Fastqsanger.gz
	SRR14295725.fastq.gz	Fastqsanger.gz

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

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

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

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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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PD-L1 AND ICOSL DISCRIMINATE HUMAN SECRETORY AND HELPER DENDRITIC CELLS IN CANCER, ALLERGY AND AUTOIMMUNITY

Project description:In this study, we define a novel phenotypic and functional dichotomy of human dendritic cells (DC), with strong relevance to cancer, allergy, and autoimmunity. Using 16 different stimuli in vitro (130 observations), we describe two states of human activated DC. PD-L1highICOSLlow Secretory DC produced large amounts of inflammatory cytokines and chemokines but induced very low levels of T helper (Th) cytokines following DC-T co-culture; conversely PD-L1lowICOSLhigh Helper DC produced low levels of secreted factors but induced high levels and a broad range of Th cytokines. Secretory DC were aligned with mature migratory LAMP3+ DC in three different cancer types, atopic dermatitis, and lupus nephritis by single-cell transcriptomics. They were associated with T cell inflammation, overexpressed stimulatory and inhibitory checkpoints, acquired increased cell-cell communication, and were associated with good prognosis in head and neck squamous cell carcinoma, and with response to checkpoint blockade in Melanoma. This functional dichotomy of DC has broad implications in inflammation and immunotherapy.

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