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IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Prdm1/Maf KO colonic CD4 T cells scRNA-seq]

ABSTRACT: IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Prdm1/Maf KO colonic CD4 T cells scRNA-seq]

PROVIDER: PRJNA667100 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12766577_1.fastq.gz	Fastqsanger.gz
	SRR12766577_2.fastq.gz	Fastqsanger.gz
	SRR12766578_1.fastq.gz	Fastqsanger.gz
	SRR12766578_2.fastq.gz	Fastqsanger.gz
	SRR12766579_1.fastq.gz	Fastqsanger.gz

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IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Prdm1/Maf KO colonic CD4 T cells scRNA-seq]

Project description:IL-27 is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, Atf3) and 2 negative (Irf9, Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10. We report two central regulators Prdm1 and Maf that cooperatively drive the expression of signature genes induced by IL-27 in Type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3+regulatory T cells. Prdm1/Maf double-knockout mice develop spontaneous colitis, phenocopying the ll10 deficient mice. Our work provides insights for IL-27 driven transcriptional networks and identifies two shared Il10 regulators that orchestrate immunoregulatory programs across T helper cell subsets.

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IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Prdm1/Maf KO Tr1 ATAC-seq]

Project description:IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Prdm1/Maf KO Tr1 ATAC-seq]

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Blimp-1 and c-Maf regulate Il10 and negatively regulate common and unique proinflammatory gene networks in IL-12 plus IL-27-driven T helper-1 cells [ATAC-Seq]

Project description:CD4+ Th1 cells producing IFN-g are required to eradicate intracellular pathogens, however if uncontrolled these cells can mediate immunopathology. The cytokine IL-10 is produced by multiple immune cells including Th1 cells during infection and regulates the immune response to minimise collateral host damage. In this study we aimed to elucidate the transcriptional network of genes controlling the expression of Il10 and proinflammatory cytokines, including Ifng in Th1 cells. We show that the transcription factors Blimp-1 and c-Maf each have unique and common effects on cytokine gene regulation and not only co-operate to induce Il10 gene expression in IL-12 plus IL-27 differentiated Th1 cells, but additionally directly negatively regulate key proinflammatory cytokines including Ifng, thus providing mechanisms for reinforcement of regulated Th1 cell responses.

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Blimp-1 and c-Maf regulate Il10 and negatively regulate common and unique proinflammatory gene networks in IL-12 plus IL-27-driven T helper-1 cells

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2022-10-31 | E-MTAB-12204 | biostudies-arrayexpress

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