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| Item Type: | Article |
|---|---|
| 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's disease patients |
| Creators Name: | Ahlers, J. and Mantei, A. and Lozza, L. and Stäber, M. and Heinrich, F. and Bacher, P. and Hohnstein, T. and Menzel, L. and Yüz, S.G. and Alvarez-Simon, D. and Bickenbach, A.R. and Weidinger, C. and Mockel-Tenbrinck, N. and Kühl, A.A. and Siegmund, B. and Maul, J. and Neumann, C. and Scheffold, A. |
| 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 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. |
| Keywords: | Crohn Disease, Inflammatory Bowel Diseases, Interleukin-10, Proto-Oncogene Proteins c-maf, STAT3 Transcription Factor, Th1 Cells / Metabolism, Animals, Mice |
| Source: | Mucosal Immunology |
| ISSN: | 1933-0219 |
| Publisher: | Nature Publishing Group |
| Volume: | 15 |
| Number: | 3 |
| Page Range: | 480-490 |
| Date: | May 2022 |
| Official Publication: | https://doi.org/10.1038/s41385-022-00487-x |
| PubMed: | View item in PubMed |
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