PT Journal AU Ahlers, J Mantei, A Lozza, L Stäber, M Heinrich, F Bacher, P Hohnstein, T Menzel, L Yüz, SG Alvarez-Simon, D Bickenbach, AR Weidinger, C Mockel-Tenbrinck, N Kühl, AA Siegmund, B Maul, J Neumann, C Scheffold, GA TI A Notch/STAT3-driven Blimp-1/c-Maf-dependent molecular switch induces IL-10 expression in human CD4+ T cells and is defective in Crohn´s disease patients SO Mucosal immunology : official journal of the Society for Mucosal Immunology JI Mucosal Immunology PY 2022 BP 480 EP 490 VL 15 IS 3 PU Elsevier BV DI 10.1038/s41385-022-00487-x WP https://macau.uni-kiel.de/receive/macau_mods_00004920 LA en DE Th1 Cells; Animals; Mice, Knockout; Humans; Mice; Inflammatory Bowel Diseases; Crohn Disease; Interleukin-10; STAT3 Transcription Factor; Proto-Oncogene Proteins c-maf SN 1933-0219 AB Immunosuppressive Interleukin (IL)-10 production by pro-inflammatory CD4+ T cells is a central self-regulatory function to limit aberrant inflammation. Still, the molecular mediators controlling IL-10 expression in human CD4+ T cells are largely undefined. Here, we identify a Notch/STAT3 signaling-module as a universal molecular switch to induce IL-10 expression across human naïve and major effector CD4+ T cell subsets. IL-10 induction was transient, jointly controlled by the transcription factors Blimp-1/c-Maf and accompanied by upregulation of several co-inhibitory receptors, including LAG-3, CD49b, PD-1, TIM-3 and TIGIT. Consistent with a protective role of IL-10 in inflammatory bowel diseases (IBD), effector CD4+ T cells from Crohn's disease patients were defective in Notch/STAT3-induced IL-10 production and skewed towards an inflammatory Th1/17 cell phenotype. Collectively, our data identify a Notch/STAT3-Blimp-1/c-Maf axis as a common anti-inflammatory pathway in human CD4+ T cells, which is defective in IBD and thus may represent an attractive therapeutic target. PI New York, NY ER