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• W2158045379 abstract "The mechanisms underlying the association between obesity and the development of asthma remain incompletely understood. Dale T. Umetsu and his colleagues report that the number of IL-17A+ type 3 innate lymphoid cells (ILCs) is increased in the lungs of mice fed a high-fat diet. Activation of the NLRP3 inflammasome in lung macrophages promotes IL-1β production and ILC development, and blockade of IL-1 signaling inhibits airway hyperreactivity in obese mice. As these ILCs are also found in the lungs of individuals with asthma, these results suggest that this pathway may be targeted in asthma. Obesity is associated with the development of asthma, which is often difficult to control. To understand the immunological pathways that lead to obesity-associated asthma, we fed mice a high-fat diet for 12 weeks, which resulted in obesity and the development of airway hyperreactivity (AHR), a cardinal feature of asthma. This AHR was independent of adaptive immunity, as it occurred in obese Rag1−/− mice, which lack B and T cells, and was dependent on interleukin-17A (IL-17A) and the NLRP3 inflammasome, as it did not develop in obese Il17a−/− or Nlrp3−/− mice. AHR was also associated with the expansion of CCR6+ type 3 innate lymphoid cells (ILCs) producing IL-17A (ILC3 cells) in the lung, which could by themselves mediate AHR when adoptively transferred into Rag2−/−; Il2rg−/− mice treated with recombinant IL-1β. Macrophage-derived IL-1β production was induced by HFD and expanded the number of lung ILC3 cells. Blockade of IL-1β with an IL-1 receptor antagonist abolished obesity-induced AHR and reduced the number of ILC3 cells. As we found ILC3-like cells in the bronchoalveolar lavage fluid of individuals with asthma, we suggest that obesity-associated asthma is facilitated by inflammation mediated by NLRP3, IL-1β and ILC3 cells." @default.
• W2158045379 created "2016-06-24" @default.
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• W2158045379 date "2013-12-15" @default.
• W2158045379 modified "2023-10-11" @default.
• W2158045379 title "Interleukin-17–producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity" @default.
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• W2158045379 doi "https://doi.org/10.1038/nm.3423" @default.
• W2158045379 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3912313" @default.
• W2158045379 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24336249" @default.
• W2158045379 hasPublicationYear "2013" @default.
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