Btnl2, or butyrophilin-like protein 2, is a member of the immunoglobulin superfamily. It has been shown to play a role in regulating T cell activation [4]. By interacting with certain immune cells, it is involved in pathways related to immune responses, potentially affecting immune homeostasis [3,4]. Given its connection to immune-related functions, understanding Btnl2 is crucial for comprehending various biological processes and disease conditions. Genetic models, such as gene knockout mouse models, have been valuable in studying its functions.

In gene knockout mouse models, Btnl2 knockout mice display decreased colonic tumorigenesis and more severe colitis phenotypes due to defective IL-22 production. Mechanistically, Btnl2 acts on group 3 innate lymphoid cells (ILC3s), CD4+ T cells, and γδ T cells to promote IL-22 production, indicating its role in colitis-associated tumorigenesis [1]. Additionally, antibody-mediated blockade of Btnl2 in murine tumour models attenuates tumour progression, suggesting it as a negative regulator of anti-tumour immunity, possibly by interacting with local γδ T cell populations to promote IL-17A production in the tumour microenvironment [2].

In conclusion, Btnl2 plays essential roles in immune-related biological processes. The study of Btnl2 knockout mouse models has revealed its significance in diseases like colitis-associated colorectal cancer and tumour immune escape. These findings provide potential therapeutic targets for treating related diseases, highlighting the importance of understanding Btnl2 in disease mechanisms and immunotherapy development [1,2].

References:

1. Peng, Qianwen, Pan, Ting, He, Ruirui, Du, Yanyun, Wang, Chenhui. 2023. BTNL2 promotes colitis-associated tumorigenesis in mice by regulating IL-22 production. In EMBO reports, 24, e56034. doi:10.15252/embr.202256034. https://pubmed.ncbi.nlm.nih.gov/36629012/

2. Du, Yanyun, Peng, Qianwen, Cheng, Du, Zhang, Zhanguo, Wang, Chenhui. 2022. Cancer cell-expressed BTNL2 facilitates tumour immune escape via engagement with IL-17A-producing γδ T cells. In Nature communications, 13, 231. doi:10.1038/s41467-021-27936-8. https://pubmed.ncbi.nlm.nih.gov/35017553/

3. Burke, Kelly P, Chaudhri, Apoorvi, Freeman, Gordon J, Sharpe, Arlene H. . The B7:CD28 family and friends: Unraveling coinhibitory interactions. In Immunity, 57, 223-244. doi:10.1016/j.immuni.2024.01.013. https://pubmed.ncbi.nlm.nih.gov/38354702/

4. Nguyen, Thang, Liu, Xikui K, Zhang, Yongliang, Dong, Chen. . BTNL2, a butyrophilin-like molecule that functions to inhibit T cell activation. In Journal of immunology (Baltimore, Md. : 1950), 176, 7354-60. doi:. https://pubmed.ncbi.nlm.nih.gov/16751379/