@Article{macau_mods_00004920, author = {Ahlers, Jonas and Mantei, Andrej and Lozza, Laura and St{\"a}ber, Manuela and Heinrich, Frederik and Bacher, Petra and Hohnstein, Thordis and Menzel, Lutz and Y{\"u}z, Simge G. and Alvarez-Simon, Daniel and Bickenbach, Anne Rieke and Weidinger, Carl and Mockel-Tenbrinck, Nadine and K{\"u}hl, Anja A. and Siegmund, Britta and Maul, Jochen and Neumann, Christian and Scheffold, Georg Alexander}, title = {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{\textasciiacute}s disease patients}, journal = {Mucosal immunology : official journal of the Society for Mucosal Immunology}, year = {2022}, publisher = {Elsevier BV}, address = {New York, NY}, volume = {15}, number = {3}, pages = {480--490}, keywords = {Th1 Cells; Animals; Mice, Knockout; Humans; Mice; Inflammatory Bowel Diseases; Crohn Disease; Interleukin-10; STAT3 Transcription Factor; Proto-Oncogene Proteins c-maf}, abstract = {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 na{\"{\i}}ve 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.}, issn = {1933-0219}, doi = {10.1038/s41385-022-00487-x}, url = {https://macau.uni-kiel.de/receive/macau_mods_00004920}, url = {https://doi.org/10.1038/s41385-022-00487-x}, url = {http://www.ncbi.nlm.nih.gov/pubmed/35169232}, file = {:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/macau_derivate_00006223/1-s2.0-S1933021922000691-main.pdf:PDF}, language = {en} }