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Updated: Jul 20, 2026
Isolation of Lung Retinoid-Containing Cells by Cell Sorting
Published on: April 11, 2025
Modulatory role for retinoid-related orphan receptor alpha in allergen-induced lung inflammation
Maisa Jaradat1, Cliona Stapleton, Stephen L Tilley
1Cell Biology Section, Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC 27599-7219, USA.
Rationale:
Nuclear receptors play a critical role in the regulation of inflammation, thus representing attractive targets for the treatment of asthma.
Objective:
In this study, we assess the potential regulatory function of retinoid-related orphan receptor alpha (RORalpha) in the adaptive immune response using ovalbumin (OVA)-induced airway inflammation as a model.
Methods:
Allergen-induced inflammation was compared between wild-type (WT) and staggerer (RORalpha(sg/sg)) mice, a natural mutant strain that is deficient in RORalpha expression.
Measurements And Main Results:
Despite robust increases in OVA-specific IgE, RORalpha(sg/sg) mice developed significantly less pulmonary inflammation, mucous cell hyperplasia, and eosinophilia compared with similarly treated WT animals. Induction of Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13, was also significantly less in RORalpha(sg/sg) mice. Microarray analysis using lung RNA showed increased expression of many genes, previously implicated in inflammation, in OVA-treated WT mice. These include mucin Muc5b, the chloride channel calcium-activated 3 (Clca3), macrophage inflammatory protein (MIP) 1alpha and 1beta, eotaxin-2, serum amyloid A3 (Saa3), and insulin-like growth factor 1 (Igf1). These genes were induced to a greater extent in OVA-treated WT mice relative to RORalpha(sg/sg) mice.
Conclusions:
Our study demonstrates that mice deficient in RORalpha exhibit an attenuated allergic inflammatory response, indicating that RORalpha plays a critical role in the development of Th2-driven allergic lung inflammation in mice, and suggests that this nuclear receptor should be further evaluated as a potential asthma target.
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