IL-1R8 is a checkpoint in NK cells regulating anti-tumor and anti-viral activity

摘要

Interleukin-1 receptor 8 (IL-1R8, also known as single immunoglobulin IL-1R-related receptor, SIGIRR, or TIR8) is a member of the IL-1 receptor (ILR) family with distinct structural and functional characteristics, acting as a negative regulator of ILR and Toll-like receptor (TLR) downstream signaling pathways and inflammation. NK cells are innate lymphoid cells which mediate resistance against pathogens and contribute to the activation and orientation of adaptive immune responses^–. NK cells mediate resistance against hematopoietic neoplasms but are generally considered to play a minor role in solid tumor carcinogenesis^–. Here we report that IL-1R8 serves as a checkpoint for NK cell maturation and effector function. Its genetic blockade unleashes NK-cell mediated resistance to hepatic carcinogenesis, hematogenous liver and lung metastasis and cytomegalovirus infection.