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

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.
Martina Molgora 1,  Eduardo Bonavita 1,  Andrea Ponzetta 1,  Federica Riva 2,  Marialuisa Barbagallo 1,  Sébastien Jaillon 1 3,  Branka Popović 4,  Giovanni Bernardini 5 6,  Elena Magrini 1,  Francesca Gianni 1,  Santiago Zelenay 7,  Stipan Jonjić 4,  Angela Santoni 5 6,  Cecilia Garlanda 1 3,  Alberto Mantovani 1 3 8
Affiliations

Affiliations

  • 1 Humanitas Clinical and Research Center, 20089 Rozzano, Italy.
  • 2 Department of Animal Pathology, Faculty of Veterinary Medicine, University of Milan, 20133 Milan, Italy.
  • 3 Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele Milan, Italy.
  • 4 Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
  • 5 Dipartimento di Medicina Molecolare Istituto Pasteur-Fondazione Cenci Bolognetti, Università di Roma "La Sapienza", 00161 Rome, Italy.
  • 6 IRCCS Neuromed, 86077 Pozzilli (IS), Italy.
  • 7 Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4QL, UK.
  • 8 The William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
PMID: 29072292 DOI: 10.1038/nature24293
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.

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