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A unique epigenomic landscape defines CD8+ tissue-resident memory T cells

ABSTRACT: A unique epigenomic landscape defines CD8+ tissue-resident memory T cells

PROVIDER: PRJNA821507 | ENA |

REPOSITORIES: ENA

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A unique epigenomic landscape defines CD8+ tissue-resident memory T cells [multiome]

Project description:A unique epigenomic landscape defines CD8+ tissue-resident memory T cells [multiome]

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A unique epigenomic landscape defines CD8+ tissue-resident memory T cells

Project description:Memory T cells provide rapid and long-term protection against infection and tumors. The memory CD8+ T cell repertoire contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. While these T cell populations have been well characterized in terms of differentiation potential and function, the epigenetic changes underlying memory T cell fate determination and tissue-residency remain largely unexplored. Here, we examined the single-cell chromatin landscape of CD8+ T cells over the course of acute viral infection. We reveal an early bifurcation of memory precursors displaying distinct chromatin accessibility and define epigenetic trajectories that lead to a circulating (TCIRC) or tissue-resident memory T (TRM) cell fate. While TRM cells displayed a conserved epigenetic signature across organs, we demonstrate that these cells exhibit tissue-specific signatures and identify transcription factors that regulate TRM cell populations in a site-specific manner. Moreover, we demonstrate that TRM cells and exhausted T (TEX) cells are distinct epigenetic lineages that are distinguishable early in their differentiation. Together, these findings show that TRM cell development is accompanied by dynamic alterations in chromatin accessibility that direct a unique transcriptional program resulting in a tissue-adapted and functionally distinct T cell state.

2022-04-02 | GSE199799 | GEO

A Unique Epigenomic Landscape Defines Human Erythropoiesis

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A Unique Epigenomic Landscape Defines Human Erythropoiesis (ATAC-seq)

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CCR8 expression defines tissue-resident memory T cells in human skin

Project description:CCR8 expression defines tissue-resident memory T cells in human skin

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The lung microenvironment results in unique gene expression and epigenomic programs in airway and parenchyma resident memory CD8 T cells

Project description:The lung microenvironment results in unique gene expression and epigenomic programs in airway and parenchyma resident memory CD8 T cells

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CCR8 expression defines tissue-resident memory T cells in human skin

Project description:Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is under strict control of T cell antigen receptor (TCR)-engagement and the skin tissue microenvironment. We here examined the relationship between CCR8+ and CCR8− T cells. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T (TRM) cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue-localization (CD103) and -retention (CD69) markers, low levels of inhibitory receptors (PD-1, Tim-3, LAG-3), and a lack of senescence markers (CD57, KLRG1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (PD-1+), senescent (CD57+, KLRG1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput analyses of expressed T cell receptor beta-chain (TRB) gene rearrangement sequences showed that the two skin memory T cell compartments distinguished by CCR8 expression are clonotypically distinct, suggesting that they are produced in response to separate antigenic challenges and distinct stimulatory conditions. Moreover, the phenotypic profiles of these populations were stable in vitro and the presence of similar levels of telomere erosion excludes the possibility of a linear differentiation pathway. In conclusion, CCR8 marks skin-specific, long-lived memory T cells. Therefore, we propose that CCR8+ T cells should be targeted in future skin vaccination research.

2017-12-11 | E-MTAB-6370 | biostudies-arrayexpress

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