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Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity

ABSTRACT: Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity

PROVIDER: PRJNA901445 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17001041.fastq.gz	Fastqsanger.gz
	SRR17001042.fastq.gz	Fastqsanger.gz
	SRR17001043.fastq.gz	Fastqsanger.gz
	SRR17001044.fastq.gz	Fastqsanger.gz
	SRR17001045.fastq.gz	Fastqsanger.gz

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Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity

Project description:Regulatory T cells (Treg cells) are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, in the present study we show that interleukin (IL)-27 is specifically produced by intestinal Treg cells to regulate helper T17 cell (TH17 cell) immunity. Selectively increased intestinal TH17 cell responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+CD62Llo Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a new Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.

2023-08-08 | GSE217949 | GEO

Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity [scRNA-Seq]

Project description:Regulatory T (Treg) cells are instrumental in establishing immunological tolerance. However, the precise effector mechanisms by which Treg cells control a specific type of immune response in a given tissue remains unresolved. By simultaneously studying Treg cells from different tissue origins under systemic autoimmunity, here we show that IL-27 is specifically produced by intestinal Treg cells to regulate Th17 immunity. Selectively increased intestinal Th17 responses in mice with Treg cell-specific IL-27 ablation led to exacerbated intestinal inflammation and colitis-associated cancer, but also helped protect against enteric bacterial infection. Furthermore, single-cell transcriptomic analysis has identified a CD83+TCF1+ Treg cell subset that is distinct from previously characterized intestinal Treg cell populations as the main IL-27 producers. Collectively, our study uncovers a novel Treg cell suppression mechanism crucial for controlling a specific type of immune response in a particular tissue, and provides further mechanistic insights into tissue-specific Treg cell-mediated immune regulation.

2023-08-08 | GSE217947 | GEO

Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity [RNA-Seq]

2023-08-08 | GSE189321 | GEO

Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity [RNA-Seq]

Project description:Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity [RNA-Seq]

| PRJNA782547 | ENA

Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity [scRNA-Seq]

Project description:Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity [scRNA-Seq]

| PRJNA901450 | ENA

Selective IL-27 production by intestinal regulatory T cells permits gut-specific regulation of Th17 immunity.

| S-EPMC9980002 | biostudies-literature

Mouse Th17 T cells, IL-23 stimulated

Project description:Interleukin 23 (IL-23) triggers pathogenic features in pro-inflammatory, IL-17-secreting T cells (Th17 and Tγδ17) that play a key role in the development of inflammatory diseases. However, the IL-23 signaling cascade remains largely undefined. Here we used quantitative phosphoproteomics to characterize IL-23 signaling in primary murine Th17 cells. We quantified 6,888 phosphorylation sites in Th17 cells, and found 168 phosphorylations regulated upom IL-23 stimulation. IL-23 increased the phosphorylation of the myosin regulatory light chain (RLC), an actomyosin contractibility marker, in Th17 and Tγδ cells. IL-23-induced RLC phosphorylation required JAK2 and ROCK catalytic activity, and the study of the IL-23/ROCK axis revealed an unexpected role of IL-23 in the migration of Tγδ17 and Th17 cells. Moreover, pharmacological inhibition of ROCK reduced Tγδ17 recruitment to inflamed skin upon challenge with inflammatory agent Imiquimod. This work: i) provides new insights into phosphorylation networks that control Th17 cells, ii) widely expands the current knowledge on IL-23 signaling, and iii) contributes to the increasing list of immune cells subsets characterized by global phosphoproteomic approaches.

2020-03-25 | PXD016633 | Pride

IL-27 production by splenic immune cells throughout persistent LCMV infection

Project description:The pleiotropic cytokine IL-27 is essential for the clearance of the persistent LCMV strain Clone 13, however the cellular sources of IL-27 during viral infection are incompletely mapped and their relative importance unknown. Here we utilised single-cell RNA-sequencing of splenocytes from IL27-p28-GFP mice infected with Clone 13 to quantify the temporal patterns of IL-27 p28 production. IL-27-p28-GFP+ and IL-27-p28-GFP- splenocytes were sorted at 4 timepoints during Clone 13 infection and analysed by 3' single-cell transcriptome sequencing. Dendritic cells were major producers of early IL-27 with macrophages and monocytes being the predominant IL-27 producers during acute and persistent phases of infection. Interestingly, we also identified activated B cells and plasma cells as a prominent subset of IL-27-producing splenocytes and through B-cell-specific deletion of IL-27-p28 demonstrated that B-cell derived IL-27 is essential for sustained function of CD4 T cells and eventual clearance of Clone 13.

2022-01-10 | GSE186898 | GEO

Interleukin-27 priming of T cells controls Interleukin-17-production in trans via induction of Programmed cell death ligand 1

Project description:Interleukin (IL)-27 is a key immunosuppressive cytokine that counters T helper 17 (Th17) cell-mediated pathology. To identify mechanisms by which IL-27 might exert its immunosuppressive effect, we analyzed genes in T cells rapidly induced by IL-27. We found that IL-27 priming of naïve T cells upregulated expression of programmed death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)1-dependent manner. When co-cultured with naïve CD4+ T cells, IL-27-primed T cells inhibited the differentiation of Th17 cells in trans through a PD-1-PD-L1 interaction. In vivo, co-administration of naïve TCR transgenic T cells (2D2 T cells) with IL-27-primed T cells expressing PD-L1 inhibited the development of Th17 cells and protected from severe autoimmune encephalomyelitis. Thus, these data identify a suppressive activity of IL-27, by which CD4+ T cells can restrict differentiation of Th17 cells in trans.

2012-07-01 | GSE38375 | GEO

The Anxiolytic Drug FGIN-1-27 Ameliorates Autoimmunity by Metabolic Reprogramming of Pathogenic Th17 Cells

Project description:CD4 T cells were treated with DMSO (control) or FGIN-1-27 under Th17 polarizing conditions and RNA sequencing was done to look at differentially expressed transcripts

2020-03-09 | GSE128308 | GEO

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