BTNL2 promotes colitis-associated tumorigenesis in mice by regulating IL-22 production

Interleukin 22 (IL-22) has an important role in colorectal tumorigenesis and many colorectal diseases such as inflammatory bowel disease and certain infections. However, the regulation of IL-22 production in the intestinal system is still unclear. Here, we present evidence that butyrophilin-like protein 2 (BTNL2) is required for colorectal IL-22 production, and BTNL2 knockout mice show decreased colonic tumorigenesis and more severe colitis phenotypes than control mice due to defective production of IL-22. Mechanistically, BTNL2 acts on group 3 innate lymphoid cells (ILC3s), CD4(+) T cells, and gamma delta T cells to promote the production of IL-22. Importantly, we find that a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and that the mBTNL2-Fc recombinant protein has a therapeutic effect in a dextran sulfate sodium (DSS)-induced colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system but also provides a potential therapeutic target for the treatment of human colorectal cancer and inflammatory bowel diseases.

Automated summary

This study reveals that BTNL2 is necessary for colorectal IL-22 production and its knockout leads to decreased colonic tumorigenesis and more severe colitis phenotypes. BTNL2 acts on ILC3s, CD4(+) T cells, and gamma delta T cells to promote IL-22 production. Importantly, a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and mBTNL2-Fc recombinant protein shows therapeutic effect in a colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system, but also provides a potential therapeutic target for human colorectal cancer and inflammatory bowel diseases.