Th22 cells control colon tumorigenesis through STAT3 and Polycomb Repression complex 2 signaling

Area of Science:

• Immunology
• Oncology
• Epigenetics

Background:

• Th22 cells are present in the colon cancer microenvironment and influence cancer stemness.
• The role of Th22 cells in colon cancer cell proliferation and apoptosis is not well understood.

Purpose of the Study:

• To investigate the interaction between Th22 cells and colon cancer cells.
• To elucidate the mechanisms by which Th22 cells affect colon cancer proliferation.

Main Methods:

• Flow cytometry, H3 thymidine incorporation, real-time PCR, and Western blotting were used to assess proliferation and gene expression.
• Chromatin immunoprecipitation (ChIP) assays and lentiviral vector-mediated shRNA transfection were employed to study signaling pathways.

Main Results:

• Th22 cells release IL-22, stimulating colon cancer cell proliferation.
• IL-22 activates STAT3, leading to increased expression of PRC2 components (SUZ12, EED).
• Activated PRC2 inhibits cell cycle checkpoint genes (p16, p21) via H3K27me3 histone methylation, promoting proliferation.

Conclusions:

• Th22 cells promote colon cancer proliferation via the IL-22/STAT3/PRC2/H3K27me3 pathway.
• This mechanism contributes to colon carcinogenesis, distinct from their role in cancer stemness.
• IL-22 levels correlate with genes controlling cancer proliferation and cell cycling in colon cancer.