IL-13 Receptor α2 Selectively Inhibits IL-13-Induced Responses in the Murine Lung

The Journal of Immunology: Official Journal of the American Association of Immunologists

Lauren Cohn¹  Buqu Hu¹  Wei Liu¹  Michael J. Grusby⁴  Sun-Young Oh⁴  Zhou Zhu⁵  Tao Zheng⁵  Robert J. Homer⁵  Jack A. Elias⁶ 

[1] and;Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115;Department of Internal Medicine and;Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224;Department of Pathology, Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06510

DOI  :  10.4049/jimmunol.180.1.522

学科分类：生物科学（综合）

来源: American Association of Immunologists

【 摘 要 】

IL-13 is a critical cytokine at sites of Th2 inflammation. In these locations it mediates its effects via a receptor complex, which contains IL-4Rα and IL-13Rα1. A third, high-affinity IL-13 receptor, IL-13Rα2, also exists. Although it was initially felt to be a decoy receptor, this has not been formally demonstrated and the role(s) of this receptor has recently become controversial. To define the role(s) of IL-13Rα2 in IL-13-induced pulmonary inflammation and remodeling, we compared the effects of lung-targeted transgenic IL-13 in mice with wild-type and null IL-13Rα2 loci. We also investigated the effect of IL-13Rα2 deficiency on the OVA-induced inflammatory response. In this study, we show that in the absence of IL-13Rα2, IL-13-induced pulmonary inflammation, mucus metaplasia, subepithelial fibrosis, and airway remodeling are significantly augmented. These changes were accompanied by increased expression and production of chemokines, proteases, mucin genes, and TGF-β1. Similarly, an enhanced inflammatory response was observed in an OVA-induced phenotype. In contrast, disruption of IL-13Rα2 had no effect on the tissue effects of lung-targeted transgenic IL-4. Thus, IL-13Rα2 is a selective and powerful inhibitor of IL-13-induced inflammatory, remodeling, and physiologic responses in the murine lung.

【 授权许可】

CC BY