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

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-?1 promotes the differentiation of Th17 cells, which are known to be a major source of IL-22, but the effect of TGF-? 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-?1 in colorectal cancer compared to normal adjacent tissue, whereas the frequency of IL-22 single producing cells is not changed. Accordingly, TGF-? 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-? signaling. We show that TGF-?, via AhR induction, and PI3K signaling promotes IL-22 production in Th17 cells.

SUBMITTER: Perez LG 

PROVIDER: S-EPMC7248087 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature