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Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity
Authors
Kim, Hye YoungLee, Hyun Jun
Chang, Ya-Jen
Pichavant, Muriel
Shore, Stephanie A.
Fitzgerald, Katherine A
Iwakura, Yoichiro
Israel, Elliot
Bolger, Kenneth
Faul, John
DeKruyff, Rosemarie H.
Umetsu, Dale T.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2014-01-01Keywords
Analysis of VarianceAnimals
Asthma
Carrier Proteins
Cell Proliferation
Diet, High-Fat
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Homeodomain Proteins
Inflammasomes
Interleukin-17
Interleukin-1beta
Lymphocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
Reverse Transcriptase Polymerase Chain Reaction
Cells
Circulatory and Respiratory Physiology
Immunity
Immunology and Infectious Disease
Immunology of Infectious Disease
Infectious Disease
Respiratory System
Metadata
Show full item recordAbstract
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.Source
Nat Med. 2014 Jan;20(1):54-61. doi: 10.1038/nm.3423. Epub 2013 Dec 15. Link to article on publisher's siteDOI
10.1038/nm.3423Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34967PubMed ID
24336249Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/nm.3423