@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}
}