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Heterogeneity of CD8αα intraepithelial lymphocytes is transcriptionally conserved between TCRαβ and TCRγδ cells

ABSTRACT: Heterogeneity of CD8αα intraepithelial lymphocytes is transcriptionally conserved between TCRαβ and TCRγδ cells

PROVIDER: PRJNA1200709 | ENA |

REPOSITORIES: ENA

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Heterogeneity of CD8αα intraepithelial lymphocytes is transcriptionally conserved between TCRαβ and TCRγδ cells

Project description:Intestinal intraepithelial lymphocytes (IELs) are a versatile population of immune cells with both effector and regulatory roles in gut immunity. Although this functional diversity is thought to arise from distinct IEL subpopulations, the heterogeneity of TCRαβ+ and TCRγδ+ IELs have not been well-characterized. Here, we sorted small intestinal IELs from Vil1 Cre+ R26 ZsGreen+ mice into four groups based on expression of either TCR or TCR and fluorescence intensity of ZsGreen and performed scRNAseq. We identified CD8αα+ T cell subsets with memory-like (Tcf7⁺) and effector-like (Prdm1⁺) profiles in both TCRαβ+ and TCRγδ+ IELs. Using CD160 and CD122 as markers of memory-like and effector-like cells, respectively, we found that while effector-like cells dominated the small intestine, memory-like IELs were more prevalent in the large intestine, suggesting a functional specialization of immune responses along the gut. Further transcriptional analysis revealed shared profiles between TCRαβ+ and TCRγδ+ small intestinal IEL subsets, suggesting conserved functional roles across these populations. Finally, our analysis indicated that TCRαβ+ memory-like IELs arise from Tcf7⁺ double-negative (DN) precursors, and that effector-like IELs subsequently differentiate from the memory-like population. In contrast, TCRγδ+ IELs appear to originate from two distinct precursor populations, one expressing Tcf7 and the other Zeb2, indicating the presence of parallel developmental pathways within this lineage. Overall, our findings reveal that both TCRαβ+ and TCRγδ+ cells contain memory-like and effector-like subsets, which may contribute to the functional heterogeneity of IELs.

2025-08-27 | GSE284856 | GEO

BCL6 is required for the thymic development of TCRαβ+CD8αα+ intraepithelial lymphocyte lineage

Project description:TCRαβ+CD8αα+ intraepithelial lymphocytes (CD8αα+ αβ IELs), a specialized subset of T cells in the gut epithelium, develop from thymic agonist-selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in nearly the absence of CD8αα+ αβ IELs. BCL6 was expressed by approximately 50% of CD8αα+ αβ IELs but the majority thymic PD1+ IELps post agonist selection; its deficiency blocked early IELp generation in the thymus. Moreover, BCL6 expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4+CD8+ double positive (DP) thymocytes exhibited increased apoptosis during agonist selection, and impaired IELp differentiation and maturation. Taken together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα+ αβ IELs.

2024-02-26 | GSE248163 | GEO

Kdm6b is required for the maturation and function of intestinal TCRβ+CD8αα+ intraepithelial lymphocytes

Project description:To under the role of Kdm6b in the regulation of intestinal TCRβ+CD8αα+ intraepithelial lymphocytes (IELs), Kdm6b was conditionally deleted in mouse T cells. Small intestinal TCRβ+CD8αα+ IELs were sorted by flow cytometry and RNA-seq was conducted to identify the differentially expressed genes.

2022-08-02 | GSE154444 | GEO

Gene expressions of TCRαβ+ CD8αα+ intraepithelial lymphocyte (IELs) in the small intestine with or without Rbpj gene

Project description:cDNA microarray data of TCRαβ+ CD8αα+ IELs in the small intestine with or without Rbpj gene

2019-06-10 | GSE117122 | GEO

Comprehensive proteomics analyses of IL-15 driven activation of intestinal intraepithelial lymphocytes

Project description:Intestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect the gut from pathogens and maintain intestinal homeostasis. The cytokine IL-15 is trans-presented by epithelial cells to IEL in complex with the IL-15 receptor α chain (IL-15Rα) and plays essential roles both in maintaining IEL homeostasis, and in inducing IEL activation in response to epithelial stress. When overproduced, IL-15 is a key driver of the gluten-induced enteropathy Coeliac disease, through cytotoxic activation of IEL. To better understand how IL-15 directly regulates both homeostatic and inflammatory functions of IEL, we performed quantitative proteomics of IL-15/Rα-stimulated murine IEL, sorted into their 3 main subpopulations, TCRγδ CD8αα, TCRαβ CD8αβ and TCRαβ CD8αα expressing IEL. The data reveal that high IL-15/Rα stimulation licenses cell cycle activation, upregulates the biosynthetic machinery in IEL, increases mitochondrial respiratory capacity and induces expression of cell surface immune receptors and adhesion proteins that potentially drive IEL activation.

2021-05-10 | PXD025891 | Pride

Tissue adaptation is the dominant driver of the proteomic landscape of intestinal intraepithelial lymphocytes

Project description:Intestinal intraepithelial T lymphocytes (T-IEL) patrol the single layer of epithelial cells lining the gut, and consist of both induced T-IEL, derived from systemic antigen-experienced lymphocytes, and natural IEL, that are developmentally targeted to the intestine. To gain functional insights into these enigmatic cells, we used high-resolution quantitative mass spectrometry to investigate the proteomic landscape of the main T-IEL populations in the gut. Comparing the proteomes of induced T-IEL, tissue-resident memory TCRαβ+ CD8αβ+ cells and natural TCRγδ+ CD8αα+ and TCRαβ+ CD8αα+ T-IEL, with naive CD8+ T cells from lymph nodes reveals striking similarities between T-IEL subsets and the dominant effect of the gut environment on T-IEL phenotypes. Analysis of copy numbers/cell of >7000 proteins provides new understanding of the differences in composition of T cell antigen receptor signal transduction pathways in T-IEL versus conventional T cells and reveals skewing of the metabolic machinery towards an exhausted T cell phenotype adapted to the intestinal environment. This study provides a resource for exploring and understanding how multiple inputs are integrated into T-IEL function.

2021-03-15 | PXD023140 | Pride

BCL6 is required for the thymic development of TCRαβ+CD8αα+ intraepithelial lymphocyte lineage

Project description:BCL6 is required for the thymic development of TCRαβ+CD8αα+ intraepithelial lymphocyte lineage

| PRJNA1041854 | ENA

Genome-wide maps of chromatin state in mouse small intestinal intraepithelial lymphocytes.

Project description:We performed CUT&Tag-Seq against histone H3K27me3 in mouse small intestinal TCRβ+CD8αα+ intraepithelial lymphocytes (IELs) of wild-type mice to analyze epigenetic modifications.

2022-08-02 | GSE185798 | GEO

Gene expressions of TCRαβ+ CD8αα+ intraepithelial lymphocyte (IELs) in the small intestine with or without Rbpj gene

Project description:Gene expressions of TCRαβ+ CD8αα+ intraepithelial lymphocyte (IELs) in the small intestine with or without Rbpj gene

| PRJNA481164 | ENA

Kdm6b is required for the maturation and function of intestinal TCRβ+CD8αα+ intraepithelial lymphocytes

Project description:Kdm6b is required for the maturation and function of intestinal TCRβ+CD8αα+ intraepithelial lymphocytes

| PRJNA646270 | ENA