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

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.

• Authors: Martina Molgora, Eduardo Bonavita, Andrea Ponzetta, Federica Riva, Marialuisa Barbagallo, Sébastien Jaillon, Branka Popović, Giovanni Bernardini, Elena Magrini, Francesca Gianni, Santiago Zelenay, Stipan Jonjić, Angela Santoni, Cecilia Garlanda, Alberto Mantovani
• Journal: Nature (Nature) Vol. 551 Issue 7678 Pg. 110-114 (11 02 2017) ISSN: 1476-4687 [Electronic] England
• PMID: 29072292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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