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

PEREZ, LAURA GARCIA; KEMPSKI, JAN; MCGEE, HEATHER M.; PELZCAR, PENELOPE; AGALIOTI, THEODORA; GIANNOU, ANASTASIOS; KONCZALLA, LEONIE; BROCKMANN, LEONIE; WAHIB, RAMEZ; XU, HAO; VESELY, MARIA CAROLINA AMEZCUA; SOUKOU, SHIWA; STEGLICH, BABETT; BEDKE, TANJA; MANTHEY, CAROLIN; SEIZ, OLIVER; DIERCKS, BJÖRN-PHILIPP; GNAFAKIS, STYLIANOS; GUSE, ANDREAS H.; PEREZ, DANIEL; IZBICKI, JAKOB R.; GAGLIANI, NICOLA; FLAVELL, RICHARD A.; HUBER, SAMUEL

NATURE COMMUNICATIONS

nature

Año: 2020 vol. 11

2041-1723

L-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.