Interleukin-17–producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity

Abstract

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.

DOI: 10.1038/nm.3423
02004006002014201520162017
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@article{Kim2014Interleukin17producingIL, title={Interleukin-17–producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity}, author={Hye Young Kim and Hyun Jun Lee and Ya-Jen Chang and Muriel Pichavant and Stephanie A. Shore and Katherine A. Fitzgerald and Yoichiro Iwakura and Elliot Israel and Kenneth Bolger and John L . Faul and Rosemarie H Dekruyff and Dale T . Umetsu}, journal={Nature Medicine}, year={2014}, volume={20}, pages={54-61} }