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Clonotypic analysis of protective influenza M2e-specific lung resident T helper memory cells reveals extensive functional plasticity

ABSTRACT: Clonotypic analysis of protective influenza M2e-specific lung resident T helper memory cells reveals extensive functional plasticity

PROVIDER: PRJNA679951 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13103010.fastq.gz	Fastqsanger.gz
	SRR13103011.fastq.gz	Fastqsanger.gz
	SRR13103012.fastq.gz	Fastqsanger.gz
	SRR13103013.fastq.gz	Fastqsanger.gz
	SRR13103014.fastq.gz	Fastqsanger.gz

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Clonotypic analysis of protective influenza M2e-specific lung resident T helper memory cells reveals extensive functional plasticity

Project description:Intranasal influenza immunization with CTA1-3M2e-DD stimulated M2e-specific Th17 tissue resident memory (Trm) cells that conferred strong antibody-independent protection against infection at 6 months after priming. These cells rapidly expanded in the lung upon infection and effectively restricted virus replication. Single-cell RNAseq transcriptomic and TCR VDJ-analysis of M2e- tetramer-sorted Trm cells on day 3 and 8 post infection revealed complete Th17-lineage dominance (no Th1, Tfh or Foxp3+ Tregs) with extensive functional plasticity involving cytotoxicity (ThCTL) as well as regulatory functions. Unexpectedly, the same clonotype hosted cells with different Th17 subcluster functions (IL-17, IL-22), Tr1 cells and ThCTLs, suggesting a tissue and context-dependent differentiation of reactivated Th17 Trm cells. A gene set enrichment analysis demonstrated up- regulation of regulatory genes in the day 8 recovery phase. Contrary to present thinking lung M2e- specific Th17 Trm cells are sufficient for controlling infection and for preventing tissue injury. These findings will have strong implications for vaccine development.

2022-06-29 | GSE161938 | GEO

Clonotypic analysis of protective influenza M2e-specific lung resident Th17 memory cells reveals extensive functional diversity.

Project description:The fate of tissue-resident memory CD4 T cells (Trm) has been incompletely investigated. Here we show that intranasal, but not parenteral, immunization with CTA1-3M2e-DD stimulated M2e-specific Th17 Trm cells, which conferred strong protection against influenza virus infection in the lung. These cells rapidly expanded upon infection and effectively restricted virus replication as determined by CD4 T cell depletion studies. Single-cell RNAseq transcriptomic and TCR VDJ-analysis of M2e-tetramer-sorted CD4 T cells on day 3 and 8 post infection revealed complete Th17-lineage dominance (no Th1 or Tregs) with extensive functional diversity and expression of gene markers signifying mature resident Trm cells (Cd69, Nfkbid, Brd2, FosB). Unexpectedly, the same TCR clonotype hosted cells with different Th17 subcluster functions (IL-17, IL-22), regulatory and cytotoxic cells, suggesting a tissue and context-dependent differentiation of reactivated Th17 Trm cells. A gene set enrichment analysis demonstrated up-regulation of regulatory genes (Lag3, Tigit, Ctla4, Pdcd1) in M2e-specific Trm cells on day 8, indicating a tissue damage preventing function. Thus, contrary to current thinking, lung M2e-specific Th17 Trm cells are sufficient for controlling infection and for protecting against tissue injury. These findings will have strong implications for vaccine development against respiratory virus infections and influenza virus infections, in particular.

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Characterization of lung tissue-resident helper T cells

Project description:Characterization of lung tissue-resident helper T cells

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Transcriptional profiling for lung tissue-resident helper T cell and spleen follicular T cells

Project description:We reported hybrid CD4+ T cell population following influenza viru infection. The hybrid CD4+ T cells exhibit both tissue residency and follicular helper T cell features. To further charaterization, we sorted lung tissue-resident helper T (TRH or TTH) cells (CD45iv-CD4+CD44+GITR-PD1hiFR4hi), non-TRH (CD45iv-CD4+CD44+GITR-PD1lowFR4low), spleen follicalar helper T (TFH) cells (CD4+CD44+GITR-PD1hiCXCR5hi) and non-TFH cells (CD4+CD44+GITR-PD1lowCXCR5low). Then the cells were applied for RNA sequencing. At the resut, we showed tissue-residency related genes are highly enriched in lung TRH but not spleen TFH cells. And The lung TRH cells express higher levels of TFH-related genes than lung-non TRH cells. Therefore, we suggest TRH cells play a role as tissue-resident helper T cells.

2020-11-27 | GSE153226 | GEO

Characterization of lung tissue-resident helper T cells

Project description:To identify the characters of tissue resident CD4 T cells following influenza virus infection, we sorted lung CD45iv-CD4+CD44hi T cells from influenza PR8 infected mice (28 d.p.i.). Then the cells were performed single cell RNA sequencing. At the result, we found clera 5 differnt clusters and each cluster represent different helper T cell types including TH1, TH17 and Treg. One cluster exhibited both tissue residency and TFH cell features. So, we identify the characters of this hybrid lung CD4 T cells.

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Peripheral blood T helper cells circulate with pathogenic tissue resident T helper cells in chronic GVHD

Project description:Peripheral blood T helper cells circulate with pathogenic tissue resident T helper cells in chronic GVHD

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Human T follicular helper cells seed the germinal center-resident regulatory pool

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Peripheral blood T helper cells circulate with pathogenic tissue resident T helper cells in chronic GVHD

Project description:Chronic graft versus host disease (cGVHD) is a systemic autoimmune-like syndrome. The role of Tph cells in the pathogenesis of cGVHD has not been examined, although previous studies have shown that cGVHD is characterized by loss of Tfh cells. Here, we show that in cGVHD patients and in a murine model that reflects characteristic features of human cGVHD, the proportions of Tph cells among CD4+ T cells in the blood were expanded. These cells augmented memory B cell differentiation and production of IgG via IL-21. Adoptive transfer experiments showed recirculation between Tph in the blood and tissue-resident T helper (Trh) cells in GVHD target tissues. The TCR repertoires of blood Tph cells and Trh cells in GVHD target tissues of mice were highly overlapping.

2023-02-22 | GSE200520 | GEO

Locally renewing resident synovial macrophages provide a protective barrier for the joint

Project description:Locally renewing resident synovial macrophages provide a protective barrier for the joint

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