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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

ABSTRACT: 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

PROVIDER: PRJNA812044 | ENA |

REPOSITORIES: ENA

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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.

2023-08-24 | GSE197782 | GEO

Blimp-1 and c-Maf regulate common and unique gene networks to protect against distinct pathways of pathobiont-induced colitis [RNA-Seq]

Project description:Using single-cell RNA-seq of colon lamina propria leukocytes (LPL), together with ATAC-seq, ChIP-seq and RNA-seq from colon LPL and sorted CD4+ T from colon lamina propria during oral infection with the pathobiont Helicobacter hepaticus we show that Blimp-1 and c-Maf both positively regulate Il10 gene expression, but also cooperate to negatively regulate a large network of proinflammatory effector genes in T cells. While T cell-specific deletion of either Prdm1, Maf or both transcription factors did not result in overt inflammation of the colon at steady state, H. hepaticus infection resulted in mild/moderate colitis in both the Prdm1fl/flCd4Cre and Maffl/flCd4Cre single T cell-specific transcription factor deficient mice, while the double knockout Prdm1fl/flMaffl/flCd4Cre infected mice suffered severe colitis and showed a massive increase in T cell effector genes in colonic LPL. Blimp-1 and c-Maf cooperate to negatively regulate genes including Ifng, Csf2, Il23r, Stat4, Il18r1 and Il2rg, and deletion of both these transcription factors in T cells translated to an exacerbated pathogenic TH1, IFN-g+GM-CSF+ effector cell response. c-Maf, additionally negatively regulated Il17a expression which was elevated in the LPL as assessed by bulk RNA-seq and scRNA-Seq analysis in the H. hepaticus infected Maffl/flCd4Cre mice.

2024-02-18 | GSE240421 | GEO

Blimp-1 and c-Maf regulate common and unique immune gene networks to protect against distinct pathways of pathobiont-induced colitis [ATAC-Seq]

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Blimp-1 and c-Maf regulate common and unique immune gene networks to protect against distinct pathways of pathobiont-induced colitis [scRNA-Seq]

2024-02-18 | GSE240419 | GEO

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: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]

| PRJNA812040 | ENA

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 [in vitro]

Project description: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 [in vitro]

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Blimp-1 and c-Maf regulate common and unique immune gene networks to protect against distinct pathways of pathobiont-induced colitis [bulk tissue RNA-seq]

Project description:Using single-cell RNA-seq and bulk tissue RNA-seq of colon lamina propria leukocytes (LPL), together with ATAC-seq, ChIP-seq and RNA-seq from colon LPL and sorted CD4+ T from colon lamina propria during oral infection with the pathobiont Helicobacter hepaticus we show that Blimp-1 and c-Maf both positively regulate Il10 gene expression, but also cooperate to negatively regulate a large network of proinflammatory effector genes in T cells. While T cell-specific deletion of either Prdm1, Maf or both transcription factors did not result in overt inflammation of the colon at steady state, H. hepaticus infection resulted in mild/moderate colitis in both the Prdm1fl/flCd4Cre and Maffl/flCd4Cre single T cell-specific transcription factor deficient mice, while the double knockout Prdm1fl/flMaffl/flCd4Cre infected mice suffered severe colitis and showed a massive increase in T cell effector genes in colonic LPL. Blimp-1 and c-Maf cooperate to negatively regulate genes including Ifng, Csf2, Il23r, Stat4, Il18r1 and Il2rg, and deletion of both these transcription factors in T cells translated to an exacerbated pathogenic TH1, IFN-g+GM-CSF+ effector cell response. c-Maf, additionally negatively regulated Il17a expression which was elevated in the LPL as assessed by bulk RNA-seq and scRNA-Seq analysis in the H. hepaticus infected Maffl/flCd4Cre mice.

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IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets [IL10+ vs IL10-T helper cell RNA-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 [in vitro]

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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]

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