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

Nature. 2017 Nov 2;551(7678):110-114. doi: 10.1038/nature24293. Epub 2017 Oct 25.

Abstract

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 signalling pathways and inflammation. Natural killer (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 haematopoietic neoplasms but are generally considered to play a minor role in solid tumour 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, haematogenous liver and lung metastasis, and cytomegalovirus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Female
  • Herpesviridae Infections / genetics
  • Herpesviridae Infections / immunology
  • Humans
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology*
  • Lymphocyte Activation / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muromegalovirus / immunology*
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / immunology
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / immunology*

Substances

  • Receptors, Interleukin-1
  • SIGIRR protein, human
  • SIGIRR protein, mouse