Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity
AuthorsKim, Hye Young
Lee, Hyun Jun
Shore, Stephanie A.
Fitzgerald, Katherine A.
DeKruyff, Rosemarie H.
Umetsu, Dale T.
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
KeywordsAnalysis of Variance
Enzyme-Linked Immunosorbent Assay
Mice, Inbred C57BL
Reverse Transcriptase Polymerase Chain Reaction
Circulatory and Respiratory Physiology
Immunology and Infectious Disease
Immunology of Infectious Disease
MetadataShow full item record
AbstractObesity 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.
SourceNat Med. 2014 Jan;20(1):54-61. doi: 10.1038/nm.3423. Epub 2013 Dec 15. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/34967
Related ResourcesLink to Article in PubMed