Resistin-like molecule-α regulates IL-13-induced chemokine production but not allergen-induced airway responses

Ariel Munitz, Eric T. Cole, Danielle Karo-Atar, Fred D. Finkelman, Marc E. Rothenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Resistin-likemolecule α (Relm-α) is one of themost up-regulated gene products in allergen- and parasite-associated Th2 responses. Localized to alternatively activated macrophages, Relm-α was shown to exert an anti-inflammatory effect in parasite-induced Th2 responses, but its role in experimental asthma remains unexplored. Here, we analyzed the cellular source, the IL-4 receptors required to stimulate Relm-α production, and the role of Relm-α after experimental asthma induction by IL-4, IL-13, ormultiple experimental regimes, including ovalbumin and Aspergillus fumigatus immunization. We demonstrate that Relm-α was secreted into the airway lumen, dependent on both the IL-13 receptor-α1 chain and likely the Type I IL-4 receptor, and differentially localized to epithelial cells andmyeloid cells, depending on the specific cytokine or aeroallergen trigger. Studies performed with Retnla gene-targeted mice demonstrate that Relm-α was largely redundant interms of inducing the infiltration of Th2 cytokines,mucus, and inflammatory cells into the lung. These results mirror the dispensable role that other alternatively activated macrophage products (such as arginase 1) have in allergen-induced experimental asthma and contrast with their role in the setting of parasitic infections. Taken together, our findings demonstrate the distinct utilization of IL-4/IL-13 receptors for the induction of Relm-α in the lungs. The differential regulation of Relm-α expression is likely determined by the relative expression levels of IL-4, IL-13, and their corresponding receptors,which are differentially expressed by divergent cells (i.e., epithelial cells and macrophages.) Finally, we identify a largely redundant functional role for Relm-α in acute experimental models of allergen-associated Th2 immune responses.

Original languageEnglish
Pages (from-to)703-713
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number5
StatePublished - May 2012


  • Asthma
  • IL-13Rα1
  • IL-4
  • Resistin-like molecule-α


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