Endogenously expressed IL-13Rα2 attenuates IL-13- mediated responses but does not activate signaling in human lung fibroblasts

Sanjay Chandriani, Daryle J. DePianto, Elsa N. N'Diaye, Alexander R. Abbas, Janet Jackman, Jack Bevers, Vladimir Ramirez-Carrozzi, Rajita Pappu, Steven E. Kauder, Karen Toy, Connie Ha, Zora Modrusan, Lawren C. Wu, Harold R. Collard, Paul J. Wolters, Jackson G. Egen, Joseph R. Arron

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


IL-13 can bind to two distinct receptors: a heterodimer of IL-13Rα1/IL-4Ra and IL-13Rα2. Whereas IL-13Rα1/IL-4Rα engagement by IL-13 leads to the activation of STAT6, the molecular events triggered by IL-13 binding to IL-13Rα2 remain incompletely understood. IL-4 can bind to and signal through the IL-13Rα1/IL-4Rα complex but does not interact with IL-13Rα2. Idiopathic pulmonary fibrosis is a progressive and generally fatal parenchymal lung disease of unknown etiology with no current pharmacologic treatment options that substantially prolong survival. Preclinical models of fibrotic diseases have implicated IL-13 activity on multiple cell types, including macrophages and fibroblasts, in initiating and perpetuating pathological fibrosis. In this study, we show that IL-13, IL-4, IL-13Rα2, and IL-13-inducible target genes are expressed at significantly elevated levels in lung tissue from patients with idiopathic pulmonary fibrosis compared with control lung tissue. IL-4 and IL-13 induce virtually identical transcriptional responses in human monocytes, macrophages, and lung fibroblasts. IL-13Rα2 expression can be induced in lung fibroblasts by IL-4 or IL-13 via a STAT6-dependent mechanism, or by TNF-α via a STAT6-independent mechanism. Endogenously expressed IL-13Rα2 decreases, but does not abolish, sensitivity of lung fibroblasts to IL-13 and does not affect sensitivity to IL-4. Genome-wide transcriptional analyses of lung fibroblasts stimulated with IL-13 in the presence of Abs that selectively block interactions of IL-13 with IL-13Rα1/IL-4Rα or IL-13Rα2 show that endogenously expressed IL-13Rα2 does not activate any unique IL-13-mediated gene expression patterns, confirming its role as a decoy receptor for IL-13 signaling.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalJournal of Immunology
Issue number1
StatePublished - Jul 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Endogenously expressed IL-13Rα2 attenuates IL-13- mediated responses but does not activate signaling in human lung fibroblasts'. Together they form a unique fingerprint.

Cite this