IL-17 producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity
Kim, Hye Young
Lee, Hyun Jun
Fitzgerald, Katherine A.
DeKruyff, Rosemarie H.
Umetsu, Dale T.Note: Order does not necessarily reflect citation order of authors.
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CitationKim, H. Y., H. J. Lee, Y. Chang, M. Pichavant, S. A. Shore, K. A. Fitzgerald, Y. Iwakura, et al. 2014. “IL-17 producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity.” Nature medicine 20 (1): 54-61. doi:10.1038/nm.3423. http://dx.doi.org/10.1038/nm.3423.
AbstractObesity is associated with the development of asthma and considerable asthma-related healthcare utilization. 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 depended on innate immunity, since it occurred in obese Rag−/− mice, and on IL-17A and the NLRP3 inflammasome, since it did not develop in obese Il17−/− or Nlrp3−/− mice. The AHR was also associated with the presence in the lungs of CCR6+ innate lymphoid cells producing IL-17A (ILC3 cells), which could by themselves mediate AHR when adoptively transferred into Rag2−/− Il2rγ−/− mice. IL-1β played an important role by expanding the ILC3 cells, and treatment to block the function of IL-1β abolished obesity-induced AHR. Since we found ILC3-like cells in the bronchoalveolar lavage fluid of human patients with asthma, we suggest that obesity-associated asthma is facilitated by inflammation mediated by NLRP3, IL-1β and ILC3 cells.
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