BTNL2 通过调节 IL-22 的产生促进小鼠结肠炎相关肿瘤发生

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 γδ 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.