Btnl2, or butyrophilin-like protein 2, is a molecule belonging to the B7 family. It is known to regulate T cell activation and has been associated with multiple biological processes and diseases. It is involved in pathways related to immune responses, with its mutation linked to inflammatory autoimmune diseases such as sarcoidosis and myositis [4].

In mice, Btnl2 knockout (KO) studies have shown its significance. Btnl2-KO mice display decreased colonic tumorigenesis and more severe colitis phenotypes due to defective production of IL-22, as Btnl2 acts on group 3 innate lymphoid cells (ILC3s), CD4+ T cells, and γδ T cells to promote IL-22 production. Additionally, antibody-mediated blockade of Btnl2 attenuates tumour progression in murine tumour models, reducing the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells while facilitating cytotoxic CD8+ T cell accumulation [1,2]. Also, in non-obese diabetic (NOD) mice, in vivo administration of rBTNL2-Ig (a recombinant form) ameliorates type 1 diabetes (T1D), associated with inhibiting autoreactive T cell functions and increasing regulatory T cells generation [3].

In conclusion, Btnl2 plays a crucial role in regulating immune-related biological processes. The gene knockout mouse models have revealed its importance in diseases like colitis-associated tumorigenesis, tumour immune escape, and T1D, highlighting its potential as a therapeutic target for these and other related diseases.