Marisol Alvarez-Martinez, Luke S Cox, Claire F Pearson, William J Branchett, Probir Chakravarty, Xuemei Wu, Hubert Slawinski, Alaa Al-Dibouni, Vasileios A Samelis, Leona Gabryšová, Simon L Priestnall, Alejandro Suárez-Bonnet, Anna Mikolajczak, James Briscoe, Fiona Powrie, Anne O'Garra
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 Prdm1fl/fl Maffl/fl Cd4Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in TH 1/NK/ILC1 effector genes in LPLs, while Prdm1fl/fl Cd4Cre and Maffl/fl Cd4Cre mice exhibited moderate pathology and a less-marked type 1 effector response...
April 12, 2024: Nature Immunology