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Chromatin accessibility landscapes of WT (Rag1-/-) and BATF KO (Rag1-/-Batf-/-) ILC3s sorted from small intestine [ATAC-seq]

ABSTRACT: Chromatin accessibility landscapes of WT (Rag1-/-) and BATF KO (Rag1-/-Batf-/-) ILC3s sorted from small intestine [ATAC-seq]

PROVIDER: PRJNA705994 | ENA |

REPOSITORIES: ENA

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Chromatin accessibility landscapes of WT (Rag1-/-) and BATF KO (Rag1-/-Batf-/-) ILC3s sorted from small intestine [ATAC-seq]

Project description:Group 3 innate lymphoid cells (ILC3s) are crucial for the maintenance of host-microbiota homeostasis in gastrointestinal mucosal tissues. The mechanisms that maintain lineage identity of intestinal ILC3s, and ILC3s-mediated orchestration of microbiota and mucosal T cell immunity are elusive. Here, we identified BATF as a gatekeeper of ILC3s homeostasis in the gut. Depletion of BATF in ILC3s resulted in excessive interferon-γ production, dysbiosis, aberrant T cell immune responses and spontaneous inflammatory bowel disease (IBD), which was considerably ameliorated by removal of adaptive immunity or antibiotic treatment. Mechanistically, BATF directly regulates ILC3s identity by globally shapes chromatin landscape of ILC3s. BATF directly binds to the cis-regulatory elements of type 1 effector genes, restrains their chromatin accessibility and inhibits their expression. Conversely, BATF promotes chromatin accessibility of genes involved in MHCII antigen processing and presentation pathways. Collectively, our findings reveal BATF is a promising candidate to maintain ILC3s stability and coordinate ILC3s–mediated control of intestinal homeostasis.

2022-08-31 | GSE168078 | GEO

ChIP-seq analysis of BATF in ILC3s sorted from small intestine of Rag1-/- mice [CUT&TAG ChIPseq]

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ChIP-seq analysis of BATF in ILC3s sorted from small intestine of Rag1-/- mice [CUT&TAG ChIPseq]

Project description:ChIP-seq analysis of BATF in ILC3s sorted from small intestine of Rag1-/- mice [CUT&TAG ChIPseq]

| PRJNA705995 | ENA

Chromatin accessibility landscapes of WT (GFP-) and BATF KO (GFP+) ILC3s sorted from lung mature ILC2s

Project description:Chromatin accessibility landscapes of WT (GFP-) and BATF KO (GFP+) ILC3s sorted from lung mature ILC2s

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Characterization of small intestine innate lymphoid cells of WT (Batf fl/fl) and cKO (Batf fl/fl Plzf cre+) mice using single cell RNA sequence [scRNA-seq]

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Chromatin accessibility landscapes of WT (GFP-) and BATF KO (GFP+) ILC3s sorted from lung mature ILC2s

Project description:Activated type 2 innate lymphoid cells (ILC2s) accumulate and promote inflammatory resolution and tissue repair in host defense against acute respiratory viral infections. However, the heterogeneity of ILC2s in the lung and the mechanisms by which ILC2 cells contribute to tissue repair remain elusive. Using single-cell RNA-sequencing (scRNA-seq), we identified a transcriptionally distinct ILC2 subset that showed enrichment for wound healing signature genes and the transcription factor BATF. Notably, BATF promoted the proliferation and function of ILC2s and restricted their plasticity during infection with influenza virus. In the absence of BATF, ILC2s lost their immune protective properties and obtained pathogenic ILC3-like function, which led to persist neutrophil infiltration, tissue damage and lethality. Mechanistically, BATF directly bound the cis-regulatory elements of wound healing genes, maintained their chromatin accessibility and promoted their expression. Lastly, BATF played an important role in an IL-33-ST2 feed-forward loop that supports ILC2 cell identity and function. Collectively, our findings shed light on a BATF-dependent ILC2 program, thereby providing a potential therapeutic target for terminating detrimental inflammation during acute viral infection.

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Bulk RNA sequencing of WT (Batf fl/fl) and Batf-/- (Batf fl/fl PLZFcre+) ILC3s sorted from small intestine [bulk RNA-seq]

Project description:Bulk RNA sequencing of WT (Batf fl/fl) and Batf-/- (Batf fl/fl PLZFcre+) ILC3s sorted from small intestine [bulk RNA-seq]

| PRJNA705992 | ENA

Chromatin accessibility landscapes of intestinal WT Nkp46-CC6- ILC3 (Double Negative, DN ILC3) and BATF-deficient cKO DN ILC3s sorted from intestine

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