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ScRNAseq of human blood, tonsil, lung and small intestine innate lymphoid cells

ABSTRACT: scRNAseq of human blood, tonsil, lung and small intestine innate lymphoid cells

PROVIDER: PRJNA1003807 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25582842_1.fastq.gz	Fastqsanger.gz
	SRR25582842_2.fastq.gz	Fastqsanger.gz
	SRR25582843_1.fastq.gz	Fastqsanger.gz
	SRR25582843_2.fastq.gz	Fastqsanger.gz
	SRR25582844.fastq.gz	Fastqsanger.gz

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Project description:Interleukin (IL)-2 is a pleiotropic cytokine that is necessary to prevent chronic inflammation in the gastrointestinal tract. The protective effects of IL-2 involve the generation, maintenance and function of regulatory T cells (Tregs), and low-dose IL-2 has emerged as a potential therapeutic strategy in inflammatory bowel disease (IBD) patients. However, the cellular and molecular pathways that control the production of IL-2 in the context of intestinal health are undefined. Here we identify that IL-2 is acutely required to maintain Tregs and immunologic homeostasis throughout the gastrointestinal tract. Strikingly, lineage-specific deletion of IL-2 in T cells could recapitulate these phenotypes in the large intestine, but not in the small intestine. Unbiased analyses revealed that group 3 innate lymphoid cells (ILC3) are the dominant cellular source of IL-2 in the small intestine, which is selectively induced by IL-1β. Macrophages produce IL-1β in the small intestine and activation of this pathway involves MyD88- and Nod2-dependent sensing of the microbiota. Loss-of-function studies defined that ILC3-derived IL-2 is essential to maintain Tregs, immunologic homeostasis and oral tolerance to dietary antigens uniquely in the small intestine. Furthermore, ILC3 production of IL-2 was significantly reduced in the small intestine of Crohn’s disease patients, and this correlated with diminished Tregs. Collectively, these results reveal a previously unappreciated pathway whereby a microbiota- and IL-1β-dependent axis promotes ILC3 production of IL-2 to orchestrate immune regulation in the small intestine.

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