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Homeostatic defects in interleukin 18‐deficient mice contribute to protection against the lethal effects of endotoxin
Author(s) -
Andrews Daniel M,
Chow Melvyn T,
Ma Yuting,
Cotterell Claire L,
Watt Sally V,
Anthony Desiree A,
Akira Shizuo,
Iwakura Yoichiro,
Trapani Joseph A,
Zitvogel Laurence,
Smyth Mark J
Publication year - 2011
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2010.168
Subject(s) - immunology , innate immune system , biology , interleukin 15 , homeostasis , cytokine , lipopolysaccharide , immune system , inflammation , interleukin , microbiology and biotechnology , immunity , interleukin 12 , cytotoxic t cell , in vitro , biochemistry
Toll‐like receptor‐4‐lipopolysaccharide (LPS)‐mediated inflammation is used to delineate signals involved in cross‐talk between antigen‐presenting cells (APCs) and lymphocytes such as natural killer (NK) cells. Following APC stimulation and cytokine release, NK cells produce interferon (IFN)‐γ. High levels of LPS induce endotoxicosis, a systemic inflammatory disease in which IFN‐γ causes significant morbidity and mortality. Several studies have highlighted the role of interleukin (IL)‐18, IL‐1β, IL‐17A and IFN‐γ in the development of endotoxicosis, but whether these cytokines interact with each other is yet to be determined. Our data demonstrate that IL‐18 and IL‐17A have important roles in NK cell IFN‐γ production during endotoxicosis. Importantly, we provide the first evidence that IL‐18 also has a role in IL‐17A production by T‐cell receptor (TCR)‐δ cells. Furthermore, we demonstrate that IL‐18‐deficient mice have a defect in γδ T‐cell homeostasis and IL‐1β production, both of which can contribute to the development of disease through induction of IL‐17A. These results reveal novel requirements for IL‐18 in innate immune cell homeostasis and activation, demonstrating that the role of IL‐18 in innate immunity occurs at a level other than activation.