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

Muriel Smet (UGent) , Lien Van Hoecke (UGent) , Ans De Beuckelaer (UGent) , Seppe Vander Beken, Thomas Naessens (UGent) , Karl Vergote (UGent) , Monique Willart (UGent) , Bart Lambrecht (UGent) , Jan-Ake Gustafsson, Knut R Steffensen, et al.
(2016) IMMUNITY INFLAMMATION AND DISEASE. 4(3). p.350-361
Author
Organization
Abstract
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 LXR and LXR isoforms (LXR-/--/-) 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 LXR-/--/- 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.
Keywords
DIETARY-CHOLESTEROL, EXPRESSION, ATHEROSCLEROSIS, INFLAMMATION, MACROPHAGES, METABOLISM, ACTIVATION, CELLS, MODEL, RISK, asthma, cholesterol, eosinophilic airway inflammation, liver X receptor

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Chicago
Smet, Muriel, Lien Van Hoecke, Ans De Beuckelaer, Seppe Vander Beken, Thomas Naessens, Karl Vergote, Monique Willart, et al. 2016. “Cholesterol-sensing Liver X Receptors Stimulate Th2-driven Allergic Eosinophilic Asthma in Mice.” Immunity Inflammation and Disease 4 (3): 350–361.
APA
Smet, Muriel, Van Hoecke, L., De Beuckelaer, A., Vander Beken, S., Naessens, T., Vergote, K., Willart, M., et al. (2016). Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice. IMMUNITY INFLAMMATION AND DISEASE, 4(3), 350–361.
Vancouver
1.
Smet M, Van Hoecke L, De Beuckelaer A, Vander Beken S, Naessens T, Vergote K, et al. Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice. IMMUNITY INFLAMMATION AND DISEASE. 2016;4(3):350–61.
MLA
Smet, Muriel, Lien Van Hoecke, Ans De Beuckelaer, et al. “Cholesterol-sensing Liver X Receptors Stimulate Th2-driven Allergic Eosinophilic Asthma in Mice.” IMMUNITY INFLAMMATION AND DISEASE 4.3 (2016): 350–361. Print.
@article{8511422,
  abstract     = {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 LXR and LXR isoforms (LXR-/--/-) 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 LXR-/--/- 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.},
  author       = {Smet, Muriel and Van Hoecke, Lien and De Beuckelaer, Ans and Vander Beken, Seppe and Naessens, Thomas and Vergote, Karl and Willart, Monique and Lambrecht, Bart and Gustafsson, Jan-Ake and Steffensen, Knut R and Grooten, Johan},
  issn         = {2050-4527},
  journal      = {IMMUNITY INFLAMMATION AND DISEASE},
  language     = {eng},
  number       = {3},
  pages        = {350--361},
  title        = {Cholesterol-sensing liver X receptors stimulate Th2-driven allergic eosinophilic asthma in mice},
  url          = {http://dx.doi.org/10.1002/iid3.118},
  volume       = {4},
  year         = {2016},
}
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