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IL-17 producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity

Obesity 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 hyperreactiv...

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Detalles Bibliográficos
Autores principales: Kim, Hye Young, Lee, 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912313/
https://www.ncbi.nlm.nih.gov/pubmed/24336249
http://dx.doi.org/10.1038/nm.3423
Descripción
Sumario:Obesity 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.