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

Laura Garcia Perez, Jan Kempski, Heather M. McGee, Penelope Pelzcar, Theodora Agalioti, Anastasios Giannou, Leonie Konczalla, Leonie Brockmann, Ramez Wahib, Hao Xu, Maria Carolina Amezcua Vesely, Shiwa Soukou, Babett Steglich, Tanja Bedke, Carolin Manthey, Oliver Seiz, Björn-Philipp Diercks, Stylianos Gnafakis, Andreas H. Guse, Daniel Perez, Jakob R. Izbicki, Nicola Gagliani, Richard A. Flavell () and Samuel Huber ()
Additional contact information
Laura Garcia Perez: University Medical Center Hamburg-Eppendorf
Jan Kempski: University Medical Center Hamburg-Eppendorf
Heather M. McGee: Salk Institute for Biological Studies
Penelope Pelzcar: University Medical Center Hamburg-Eppendorf
Theodora Agalioti: University Medical Center Hamburg-Eppendorf
Anastasios Giannou: University Medical Center Hamburg-Eppendorf
Leonie Konczalla: University Medical Center Hamburg-Eppendorf
Leonie Brockmann: Columbia University
Ramez Wahib: University Medical Center Hamburg-Eppendorf
Hao Xu: Yale University
Maria Carolina Amezcua Vesely: Yale University
Shiwa Soukou: University Medical Center Hamburg-Eppendorf
Babett Steglich: University Medical Center Hamburg-Eppendorf
Tanja Bedke: University Medical Center Hamburg-Eppendorf
Carolin Manthey: University Medical Center Hamburg-Eppendorf
Oliver Seiz: University Medical Center Hamburg-Eppendorf
Björn-Philipp Diercks: University Medical Center Hamburg-Eppendorf
Stylianos Gnafakis: Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin
Andreas H. Guse: University Medical Center Hamburg-Eppendorf
Daniel Perez: University Medical Center Hamburg-Eppendorf
Jakob R. Izbicki: University Medical Center Hamburg-Eppendorf
Nicola Gagliani: University Medical Center Hamburg-Eppendorf
Richard A. Flavell: Yale University
Samuel Huber: University Medical Center Hamburg-Eppendorf

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-16363-w

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