biostudies-literatureAlvarez-Martinez MCancer Research UKMedical Research CouncilThe Francis Crick Institute"la Caixa" FoundationWellcome Trust886-901https://www.ebi.ac.uk/biostudies/studies/S-EPMC11065689biostudies-literatureUnknown25(5)Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4⁺ T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1^fl/flMaf^fl/flCd4^Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in T_H1/NK/ILC1 effector genes in LPLs, while Prdm1^fl/flCd4^Cre and Maf^fl/flCd4^Cre mice exhibited moderate pathology and a less-marked type 1 effector respNature immunologyBlimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.PMC11065689CC2032CC1061FC001126Pearson CFSlawinski HSamelis VAChakravarty PAl-Dibouni APowrie FAlvarez-Martinez MBriscoe JSuarez-Bonnet APriestnall SLO'Garra AMikolajczak ACox LSBranchett WJGabrysova LWu XfalseBlimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4⁺ T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1^fl/flMaf^fl/flCd4^Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in T_H1/NK/ILC1 effector genes in LPLs, while Prdm1^fl/flCd4^Cre and Maf^fl/flCd4^Cre mice exhibited moderate pathology and a less-marked type 1 effector resp2024-01-01T00:00:00Z2024 May2026-06-01T21:20:52.867Z2026-05-21T03:08:19.217ZS-EPMC110656893860954710.1038/s41590-024-01814-z