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白细胞介素-1受体8（IL-1R8）是自然杀伤细胞中调节抗肿瘤和抗病毒活性的一个检查点。

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

作者信息

Molgora Martina, Bonavita Eduardo, Ponzetta Andrea, Riva Federica, Barbagallo Marialuisa, Jaillon Sébastien, Popović Branka, Bernardini Giovanni, Magrini Elena, Gianni Francesca, Zelenay Santiago, Jonjić Stipan, Santoni Angela, Garlanda Cecilia, Mantovani Alberto

机构信息

Humanitas Clinical and Research Center, 20089 Rozzano, Italy.

Department of Animal Pathology, Faculty of Veterinary Medicine, University of Milan, 20133 Milan, Italy.

出版信息

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

DOI:10.1038/nature24293
PMID:29072292
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5768243/
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.

摘要

白细胞介素-1受体8（IL-1R8，也称为单免疫球蛋白IL-1R相关受体、SIGIRR或TIR8）是白细胞介素-1受体（ILR）家族的成员，具有独特的结构和功能特征，作为ILR和Toll样受体（TLR）下游信号通路及炎症的负调节因子。自然杀伤（NK）细胞是先天性淋巴细胞，介导对病原体的抵抗，并有助于适应性免疫反应的激活和定向。NK细胞介导对造血肿瘤的抵抗，但通常被认为在实体瘤致癌过程中起次要作用。在此我们报告，IL-1R8作为NK细胞成熟和效应功能的一个检查点。其基因阻断可释放NK细胞介导的对肝癌发生、血行性肝和肺转移以及巨细胞病毒感染的抵抗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/206c040bee92/emss-74230-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/61a178d72517/emss-74230-f005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/432d1c4754a7/emss-74230-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/206c040bee92/emss-74230-f004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/7a508357231b/emss-74230-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/bd8de95a9bef/emss-74230-f009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/85e9f3d88f37/emss-74230-f010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/863eb4fcde5c/emss-74230-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14b4/5768243/c152bae2c3d1/emss-74230-f002.jpg
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