期刊
NATURE MEDICINE
卷 20, 期 1, 页码 54-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3423
关键词
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资金
- US National Institutes of Health [RO1AI068085, RO1HL62348, ES013307]
- D. and D. Bunning Food Allergy Project
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL062348] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U54AI057159, R01AI068085] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES013307] Funding Source: NIH RePORTER
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-1 beta. Macrophage-derived IL-1 beta production was induced by HFD and expanded the number of lung ILC3 cells. Blockade of IL-1 beta 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-1 beta and ILC3 cells.
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