TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer

• DOI: 10.1038/s41467-020-16363-w
• Publication Date: 2020-05-25T10:02:44Z
• Authors: Laura Garcia Perez; Jan Kempski; Heather M. McGee; Penelope Pelzcar; Theodora Agalioti; Anastasios Giannou; Leonie Konczalla; Leonie Brockmann; Ramez Wahib; Hao Xu; Maria Carolina Am...; Shiwa Soukou; Babett Steglich; Tanja Bedke; Carolin Manthey; Oliver Seiz; Björn-Philipp Die...; Stylianos Gnafakis; Andreas H. Guse; Daniel Perez; Jakob R. Izbicki; Nicola Gagliani; Richard A. Flavell; Samuel Huber
• Keywords: Male; Carcinogenesis; Science; Mice, Transgenic; Article; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; https://purl.org/becyt/ford/3.1; IL-22; Basic Helix-Loop-Helix Transcription Factors; Animals; Humans; https://purl.org/becyt/ford/3; TGFb; 0303 health sciences; Interleukins; AhR; Q; Interleukin-17; Cell Differentiation; Colitis; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Receptors, Aryl Hydrocarbon; Colonic Neoplasms; Female; Th17; Colorectal Neoplasms; Signal Transduction

IL-22 has dual functions during tumorigenesis. Short term production protects against genotoxic stress, whereas uncontrolled activity promotes tumor growth; therefore, tight regulation of is essential. TGF-β1 the differentiation Th17 cells, which are known to be a major source IL-22, but effect TGF-β signaling on in CD4+ T cells controversial. Here we show an increased presence IL-17+IL-22+ and colorectal cancer compared normal adjacent tissue, frequency single producing not changed. Accordingly, (specifically cells) emergence IL-22-producing thereby tumorigenesis mice. however, dependent signaling. We that TGF-β, via AhR induction, PI3K cells.