دورية أكاديمية
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
| العنوان: | 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 |
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| المؤلفون: | Ahlers, J., Mantei, A., Lozza, L., Stäber, M., Heinrich, F., Bacher, P., Hohnstein, T., Menzel, L., Yüz, S.G., Alvarez-Simon, D., Bickenbach, A.R., Weidinger, C., Mockel-Tenbrinck, N., Kühl, A.A., Siegmund, B., Maul, J., Neumann, C., Scheffold, A. |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2022 |
| المجموعة: | Max-Delbrueck-Center for Molecular Medicine, Berlin: MDC Repository |
| مصطلحات موضوعية: | Cancer Research, Topic 3: Integrative Biomedicine |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | http://edoc.mdc-berlin.de/21358/1/21358oa.pdfTest; http://edoc.mdc-berlin.de/21358/7/21358suppl.pdfTest; 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. 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. Mucosal Immunology 15 (3): 480-490. May 2022 |
| DOI: | 10.1038/s41385-022-00487-x |
| الإتاحة: | https://doi.org/10.1038/s41385-022-00487-xTest http://edoc.mdc-berlin.de/21358Test/ https://edoc.mdc-berlin.de/21358Test/ http://edoc.mdc-berlin.de/21358/1/21358oa.pdfTest http://edoc.mdc-berlin.de/21358/7/21358suppl.pdfTest |
| حقوق: | cc_by_4 |
| رقم الانضمام: | edsbas.D7B7464D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41385-022-00487-x |
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