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

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

doi:10.1038/nature24293

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

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

^*Corresponding author for this work

Cancer Research UK Manchester Institute

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	110-114
Number of pages	5
Journal	Nature
Volume	551
Issue number	7678
Early online date	25 Oct 2017
DOIs	https://doi.org/10.1038/nature24293
Publication status	Published - 2 Nov 2017

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title = "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.",

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T1 - IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity

AU - Molgora, Martina

AU - Bonavita, Eduardo

AU - Ponzetta, Andrea

AU - Riva, Federica

AU - Barbagallo, Marialuisa

AU - Jaillon, Sébastien

AU - Popović, Branka

AU - Bernardini, Giovanni

AU - Magrini, Elena

AU - Gianni, Francesca

AU - Zelenay, Santiago

AU - Jonjić, Stipan

AU - Santoni, Angela

AU - Garlanda, Cecilia

AU - Mantovani, Alberto

PY - 2017/11/2

Y1 - 2017/11/2

N2 - 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.

AB - 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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JO - Nature

JF - Nature

IS - 7678

ER -

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

Abstract

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