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Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE220030 | GEO | 2023/10/20

REPOSITORIES: GEO

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Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [scRNA-seq]

Project description:Intestinal intraepithelial lymphocytes (IEL) are capable of rapid innate-like responses to microenvironmental cues. While poised to activation, IEL effector functions must be stringently controlled. Aiolos is an Ikaros zinc finger (IKZF) family member encoded by Ikzf3 that promotes histone deacetylation. Here, we found that Aiolos is a crucial regulator of IEL activation. Ikzf3–/– CD8αα+ IEL expressed high levels of innate NK receptors, cytotoxic enzymes, cytokines and chemokines. Single cell RNAseq of IEL revealed that Ikzf3 deficiency mostly amplified the effector machinery of a CD8αα+ IEL subset characterized by high expression CD122, the receptor for IL-15. Furthermore, Ikzf3 deficiency increased IEL responsiveness to IL-15. Aiolos binding sites were close to those for STAT5 and RUNX transcription factors that promote IL-15 signaling and cytolytic programs, respectively; lack of Ikzf3 increased accessibility and histone acetylation of these chromatin regions. Ikzf3 deficiency increased susceptibility to colitis, demonstrating the functional relevance of Aiolos-mediated regulation of IEL effector functions.

2023-10-20 | GSE220028 | GEO

Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [CUT&RUN]

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Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [ATAC-seq]

2023-10-20 | GSE220021 | GEO

Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [RNA-seq]

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Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes

Project description:Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes

| PRJNA908085 | ENA

Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [ATAC-seq]

Project description:Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [ATAC-seq]

| PRJNA908082 | ENA

Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [CUT&RUN]

Project description:Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [CUT&RUN]

| PRJNA908089 | ENA

Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [scRNA-seq]

Project description:Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [scRNA-seq]

| PRJNA908090 | ENA

Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [RNA-seq]

Project description:Aiolos modulates IL-15 responsiveness of intestinal intraepithelial lymphocytes [RNA-seq]

| PRJNA908083 | ENA

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

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