TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer
| Autor: | Oliver Seiz, Nicola Gagliani, Carolin F. Manthey, Jan Kempski, Anastasios D. Giannou, Penelope Pelzcar, Jakob R. Izbicki, Babett Steglich, Ramez Wahib, Daniel Perez, Stylianos Gnafakis, Shiwa Soukou, Leonie Brockmann, Tanja Bedke, Andreas H. Guse, Samuel Huber, Hao Xu, Laura Garcia Perez, Theodora Agalioti, Richard A. Flavell, Heather M. McGee, Björn-Philipp Diercks, Leonie Konczalla, Maria Carolina Amezcua Vesely |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Carcinogenesis Colorectal cancer Cellular differentiation General Physics and Astronomy medicine.disease_cause Interleukin 22 Mice Phosphatidylinositol 3-Kinases 0302 clinical medicine Transforming Growth Factor beta Basic Helix-Loop-Helix Transcription Factors lcsh:Science Receptor CD4-positive T cells Multidisciplinary Chemistry Interleukin-17 Cell Differentiation Colitis Publisher Correction Cell biology Lymphocyte differentiation 030220 oncology & carcinogenesis Colonic Neoplasms Tumour immunology Female Colorectal Neoplasms Signal Transduction Science Transgene Mice Transgenic Article General Biochemistry Genetics and Molecular Biology Transforming Growth Factor beta1 03 medical and health sciences Lymphocytes Tumor-Infiltrating medicine Animals Humans Interleukins General Chemistry medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Receptors Aryl Hydrocarbon Th17 Cells lcsh:Q Transforming growth factor |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | IL-22 has dual functions during tumorigenesis. Short term IL-22 production protects against genotoxic stress, whereas uncontrolled IL-22 activity promotes tumor growth; therefore, tight regulation of IL-22 is essential. TGF-β1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-β signaling on the production of IL-22 in CD4+ T cells is controversial. Here we show an increased presence of IL-17+IL-22+ cells and TGF-β1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-β signaling in CD4+ T cells (specifically Th17 cells) promotes the emergence of IL-22-producing Th17 cells and thereby tumorigenesis in mice. IL-22 single producing T cells, however, are not dependent on TGF-β signaling. We show that TGF-β, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells. Poly-functional helper T cells can have a stronger effect than mono-functional T cells, but whether the response is qualitatively different is not clear. Here the authors show that a population of IL-17+IL-22+, but not single IL-22+, CD4+ T cells are induced by TGF-β, enriched in patients with colorectal cancer (CRC) and drive CRC progression in mice. |
| Databáze: | OpenAIRE |
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