| First Author | Kim HY | Year | 2014 |
| Journal | Nat Med | Volume | 20 |
| Issue | 1 | Pages | 54-61 |
| PubMed ID | 24336249 | Mgi Jnum | J:226577 |
| Mgi Id | MGI:5697777 | Doi | 10.1038/nm.3423 |
| Citation | Kim HY, et al. (2014) Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity. Nat Med 20(1):54-61 |
| abstractText | 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-1beta. Macrophage-derived IL-1beta production was induced by HFD and expanded the number of lung ILC3 cells. Blockade of IL-1beta 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-1beta and ILC3 cells. |
