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TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer.
- Source :
-
Nature communications [Nat Commun] 2020 May 25; Vol. 11 (1), pp. 2608. Date of Electronic Publication: 2020 May 25. - Publication Year :
- 2020
-
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.
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors metabolism
Carcinogenesis immunology
Cell Differentiation
Colitis immunology
Colonic Neoplasms immunology
Colonic Neoplasms pathology
Colorectal Neoplasms etiology
Colorectal Neoplasms immunology
Colorectal Neoplasms pathology
Disease Models, Animal
Female
Humans
Interleukin-17 genetics
Interleukin-17 metabolism
Lymphocytes, Tumor-Infiltrating immunology
Lymphocytes, Tumor-Infiltrating pathology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phosphatidylinositol 3-Kinases metabolism
Receptors, Aryl Hydrocarbon genetics
Receptors, Aryl Hydrocarbon metabolism
Signal Transduction immunology
Th17 Cells pathology
Transforming Growth Factor beta1 metabolism
Interleukin-22
Colitis complications
Colonic Neoplasms etiology
Interleukins biosynthesis
Th17 Cells immunology
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32451418
- Full Text :
- https://doi.org/10.1038/s41467-020-16363-w