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