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Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [scRNA-seq]

ABSTRACT: Pathogenic CD4+ T cells perpetuate chronic tissue inflammation, but mechanisms remain largely undefined. Here, with transcriptome, epigenome, and clonal analysis, we compared CD4+Tm subsets among the liver and lung in the No GVHD and cGVHD recipients. Four CD4+Tm subsets identified with Ly108 versus CD69 expression were compared.

ORGANISM(S): Mus musculus

PROVIDER: GSE263812 | GEO | 2025/12/11

REPOSITORIES: GEO

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Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [RNA-seq]

Project description:Pathogenic CD4+ T cells perpetuate chronic tissue inflammation, but mechanisms remain largely undefined. Here, with transcriptome, epigenome, and clonal analysis, we compared CD4+Tm subsets among the liver and lung in the No GVHD and cGVHD recipients. Four CD4+Tm subsets identified with Ly108 versus CD69 expression were compared

2025-12-11 | GSE263811 | GEO

Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [scTCR-seq]

2025-12-11 | GSE263813 | GEO

Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [ATAC-seq]

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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

Calcineurin inhibition rescues alloantigen-specific central memory T cell subsets and promotes chronic GVHD

Project description:Calcineurin inhibitors (CNIs) constitute the backbone of modern acute graft-versus-host disease (aGVHD) prophylaxis regimens but have limited efficacy in the prevention and treatment of chronic GVHD (cGVHD). We investigated the effect of CNIs on immune tolerance after stem cell transplantation with discovery-based single cell gene expression and T-cell receptor (TCR) assays of clonal immunity in tandem with traditional protein-based approaches and preclinical modeling. While CNIs suppress the clonal expansion in CD8+ T-cells, alloreactive CD4+ T-cell clusters preferentially expanded during GVHD. Moreover, CNIs mediated reversible dose-dependent suppression of T cell activation and all stages of donor T-cell exhaustion but favored the differentiation to central memory T-cells. Critically, CNIs promoted the expansion of both polyclonal and TCR-specific alloreactive central memory CD4+ T-cells with high self-renewal capacity that mediated cGVHD following drug withdrawal. In contrast to post-transplant cyclophosphamide (PT-Cy), CSA was ineffective in eliminating IL-17A-secreting alloreactive T cell clones that mediate cGVHD. Collectively, we show that although CNIs attenuate aGVHD, they paradoxically rescue alloantigen-specific central memory T-cells, especially within the CD4+ compartment in lymphoid and GVHD target tissues, thus predisposing to cGVHD. These data provide further evidence to caution against CNI-based immune suppression without concurrent approaches that eliminate alloreactive T-cell clones.

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Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [ATAC-seq]

Project description:Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [ATAC-seq]

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Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [RNA-seq]

Project description:Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [RNA-seq]

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Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [scRNA-seq]

Project description:Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [scRNA-seq]

| PRJNA1099282 | ENA

Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [scTCR-seq]

Project description:Integrated transcriptomic, epigenetic, and TCR clonality analysis of CD4⁺ Tm subsets in liver and lung during chronic GVHD in mice [scTCR-seq]

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Signatures of GVHD and Relapse after Post-Transplant Cyclophosphamide Revealed by Immune Profiling and Machine Learning [15065R]

Project description:Lymphocyte subsets (CD8, CD4 Tconv, CD4 Treg) were sorted from patients' peripheral blood obtained on day 28 after matched-donor allogeneic bone marrow transplantation followed by posttransplant cyclophosphamide (PTCy) as a single agent GVHD prophylaxis (NCT00809276). Cohort of patients developed GVHD, or remained GVHD-free. RNA-sequencing was performed to analyze the transcriptional landscape of alloresponse in post-PTCy breakthrough GVHD.

2021-09-28 | GSE182610 | GEO

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