Cholesterol‐sensing liver X receptors stimulate Th2‐driven allergic eosinophilic asthma in mice

نویسندگان

  • Muriel Smet
  • Lien Van Hoecke
  • Ans De Beuckelaer
  • Seppe Vander Beken
  • Thomas Naessens
  • Karl Vergote
  • Monique Willart
  • Bart N. Lambrecht
  • Jan‐Åke Gustafsson
  • Knut R. Steffensen
  • Johan Grooten
چکیده

INTRODUCTION Liver X receptors (LXRs) are nuclear receptors that function as cholesterol sensors and regulate cholesterol homeostasis. High cholesterol has been recognized as a risk factor in asthma; however, the mechanism of this linkage is not known. METHODS To explore the importance of cholesterol homeostasis for asthma, we investigated the contribution of LXR activity in an ovalbumin- and a house dust mite-driven eosinophilic asthma mouse model. RESULTS In both models, airway inflammation, airway hyper-reactivity, and goblet cell hyperplasia were reduced in mice deficient for both LXRα and LXRβ isoforms (LXRα(-/-)β(-/-)) as compared to wild-type mice. Inversely, treatment with the LXR agonist GW3965 showed increased eosinophilic airway inflammation. LXR activity contributed to airway inflammation through promotion of type 2 cytokine production as LXRα(-/-)β(-/-) mice showed strongly reduced protein levels of IL-5 and IL-13 in the lungs as well as reduced expression of these cytokines by CD4(+) lung cells and lung-draining lymph node cells. In line herewith, LXR activation resulted in increased type 2 cytokine production by the lung-draining lymph node cells. CONCLUSIONS In conclusion, our study demonstrates that the cholesterol regulator LXR acts as a positive regulator of eosinophilic asthma in mice, contributing to airway inflammation through regulation of type 2 cytokine production.

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عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2016