IL-13 receptor alpha2 selectively inhibits IL-13-induced responses in the murine lung.
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-4Ralpha and IL-13Ralpha1. A third, high-affinity IL-13 receptor, IL-13Ralpha2, 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-13Ralpha2 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-13Ralpha2 loci. We also investigated the effect of IL-13Ralpha2 deficiency on the OVA-induced inflammatory response. In this study, we show that in the absence of IL-13Ralpha2, 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-beta1. Similarly, an enhanced inflammatory response was observed in an OVA-induced phenotype. In contrast, disruption of IL-13Ralpha2 had no effect on the tissue effects of lung-targeted transgenic IL-4. Thus, IL-13Ralpha2 is a selective and powerful inhibitor of IL-13-induced inflammatory, remodeling, and physiologic responses in the murine lung.
Zheng
Tao
T
Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. tzheng@jhmi.edu
Liu
Wei
W
Oh
Sun-Young
SY
Zhu
Zhou
Z
Hu
Buqu
B
Homer
Robert J
RJ
Cohn
Lauren
L
Grusby
Michael J
MJ
Elias
Jack A
JA
D000818:Animals; D005355:Fibrosis; D018793:Interleukin-13 / Q000378:metabolism* / Q000494:pharmacology; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008679:Metaplasia / Q000276:immunology / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009093:Mucus; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology
D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D015847:Interleukin-4; D010047:Ovalbumin