title: Resistin-like molecule-α regulates IL-13-induced chemokine production but not allergen-induced airway responses.
abstract: Resistin-like molecule α (Relm-α) is one of the most 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, or multiple 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 and myeloid cells, depending on the specific cytokine or aeroallergen trigger. Studies performed with Retnla gene-targeted mice demonstrate that Relm-α was largely redundant in terms 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.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Munitz
authors.forename: Eric T
authors.initials: ET
authors.lastname: Cole
authors.forename: Danielle
authors.initials: D
authors.lastname: Karo-Atar
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D018793:Interleukin-13 / Q000502:physiology*; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000485:Allergens; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; C413576:Retnla protein, mouse