학술논문
Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis
Document Type
Article
Author
Alvarez-Martinez, Marisol; Cox, Luke S.; Pearson, Claire F.; Branchett, William J.; Chakravarty, Probir; Wu, Xuemei; Slawinski, Hubert; Al-Dibouni, Alaa; Samelis, Vasileios A.; Gabryšová, Leona; Priestnall, Simon L.; Suárez-Bonnet, Alejandro; Mikolajczak, Anna; Briscoe, James; Powrie, Fiona; O’Garra, Anne
Source
Nature Immunology; 20240101, Issue: Preprints p1-16, 16p
Subject
Language
ISSN
15292908; 15292916
Abstract
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 Il10while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1fl/flMaffl/flCd4Cremice infected with Helicobacter hepaticusdeveloped severe colitis with an increase in TH1/NK/ILC1 effector genes in LPLs, while Prdm1fl/flCd4Creand Maffl/flCd4Cremice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maffl/flCd4Cremice had increased type 17 responses with increased Il17aand Il22expression and an increase in granulocytes and myeloid cell numbers, resulting in increased T cell–myeloid–neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1or Maf, revealing potential mechanisms of human disease.