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Tissue-resident PSGL1loCD4+ T cells promote B cell differentiation and chronic graft-versus-host-disease-associated autoimmunity

ABSTRACT: Tissue-resident PSGL1loCD4+ T cells promote B cell differentiation and chronic graft-versus-host-disease-associated autoimmunity

PROVIDER: PRJNA661763 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12601007.fastq.gz	Fastqsanger.gz
	SRR12601008.fastq.gz	Fastqsanger.gz
	SRR12601009.fastq.gz	Fastqsanger.gz
	SRR12601010.fastq.gz	Fastqsanger.gz
	SRR12601011.fastq.gz	Fastqsanger.gz

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Tissue-resident PSGL1loCD4+ T cells promote B cell differentiation and chronic graft-versus-host disease-associated autoimmunity.

Project description:CD4+ T cell interactions with B cells play a critical role in the pathogenesis of systemic autoimmune diseases such as systemic lupus and chronic graft-versus-host disease (cGVHD). Extrafollicular CD44hiCD62LloPSGL1loCD4+ T cells (PSGL1loCD4+ T cells) are associated with the pathogenesis of lupus and cGVHD, but their causal role has not been established. With murine and humanized MHC-/-HLA-A2+DR4+ murine models of cGVHD, we showed that murine and human PSGL1loCD4+ T cells from GVHD target tissues have features of B cell helpers with upregulated expression of programmed cell death protein 1 (PD1) and inducible T cell costimulator (ICOS) and production of IL-21. They reside in nonlymphoid tissues without circulating in the blood and have features of tissue-resident memory T cells with upregulated expression of CD69. Murine PSGL1loCD4+ T cells from GVHD target tissues augmented B cell differentiation into plasma cells and production of autoantibodies via their PD1 interaction with PD-L2 on B cells. Human PSGL1loCD4+ T cells were apposed with memory B cells in the liver tissues of humanized mice and cGVHD patients. Human PSGL1loCD4+ T cells from humanized GVHD target tissues also augmented autologous memory B cell differentiation into plasma cells and antibody production in a PD1/PD-L2-dependent manner. Further preclinical studies targeting tissue-resident T cells to treat antibody-mediated features of autoimmune diseases are warranted.

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Tissue-resident PSGL1loCD4+ T cells promote B cell differentiation and chronic graft-versus-host-disease-associated autoimmunity

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