000K utf8 1100 $c2022 1500 eng 2050 urn:nbn:de:gbv:8:3-2024-00633-3 2051 10.1038/s41385-022-00487-x 3000 Ahlers, Jonas 3010 Alvarez-Simon, Daniel 3010 Bacher, Petra 3010 Bickenbach, Anne Rieke 3010 Heinrich, Frederik 3010 Hohnstein, Thordis 3010 Kühl, Anja A 3010 Lozza, Laura 3010 Mantei, Andrej 3010 Maul, Jochen 3010 Menzel, Lutz 3010 Mockel-Tenbrinck, Nadine 3010 Neumann, Christian 3010 Scheffold, Georg Alexander 3010 Siegmund, Britta 3010 Stäber, Manuela 3010 Weidinger, Carl 3010 Yüz, Simge G 4030 $nElsevier BV 4209 Immunosuppressive Interleukin (IL)-10 production by pro-inflammatory CD4+ T cells is a central self-regulatory function to limit aberrant inflammation. Still, the molecular mediators controlling IL-10 expression in human CD4+ T cells are largely undefined. Here, we identify a Notch/STAT3 signaling-module as a universal molecular switch to induce IL-10 expression across human naïve and major effector CD4+ T cell subsets. IL-10 induction was transient, jointly controlled by the transcription factors Blimp-1/c-Maf and accompanied by upregulation of several co-inhibitory receptors, including LAG-3, CD49b, PD-1, TIM-3 and TIGIT. Consistent with a protective role of IL-10 in inflammatory bowel diseases (IBD), effector CD4+ T cells from Crohn's disease patients were defective in Notch/STAT3-induced IL-10 production and skewed towards an inflammatory Th1/17 cell phenotype. Collectively, our data identify a Notch/STAT3-Blimp-1/c-Maf axis as a common anti-inflammatory pathway in human CD4+ T cells, which is defective in IBD and thus may represent an attractive therapeutic target. 4950 https://doi.org/10.1038/s41385-022-00487-x$xR$3Volltext$534 4950 https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2024-00633-3$xR$3Volltext$534 4961 https://macau.uni-kiel.de/receive/macau_mods_00004920 5051 610 5550 Animals 5550 Crohn Disease 5550 Humans 5550 Inflammatory Bowel Diseases 5550 Interleukin-10 5550 Mice 5550 Mice, Knockout 5550 Proto-Oncogene Proteins c-maf 5550 STAT3 Transcription Factor 5550 Th1 Cells