IL-11 receptor α in the pathogenesis of IL-13-induced inflammation and remodeling

Qingsheng Chen, Lesley Rabach, Paul Noble, Tao Zheng, Geun Lee Chun, Robert J. Homer, Jack A. Elias

Research output: Contribution to journalArticlepeer-review

Abstract

IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation. In Th2-dominant inflammatory disorders such as asthma, IL-11 is simultaneously induced. However, the relationship(s) between IL-11 and IL-13 in these responses has not been defined, and the role(s) of IL-11 in the genesis of the tissue effects of IL-13 has not been evaluated. We hypothesized that IL-11, signaling via the IL-11Rα-gp130 receptor complex, plays a key role in IL-13-induced tissue responses. To test this hypothesis we compared the expression of IL-11, IL-11Rα, and gp130 in tangs from wild-type mice and transgenic mice in which IL-13 was overexpressed in a tang-specific fashion. We simultaneously characterized the effects of a null mutation of IL-11Rα on the tissue effects of transgenic IL-13. These studies demonstrate that IL-13 is a potent stimulator of DL-11 and IL-11Rα. They also demonstrate that IL-13 is a potent stimulator of inflammation, fibrosis, hyaluronic acid accumulation, myofibroblast accumulation, alveolar remodeling, mucus metaplasia, and respiratory failure and death in mice with wild-type IL-11Rα loci and that these alterations are ameliorated in the absence of IL-11Rα. Lastly, they provide insight into the mechanisms of these processes by demonstrating that IL-13 stimulates CC chemokines, matrix metalloproteinases, mucin genes, and gob-5 and stimulates and activates TGF-β1 via IL-11Rα-dependent pathways. When viewed in combination, these studies demonstrate that IL-11Rα plays a key role in the pathogenesis of IL-13-ieduced inflammation and remodeling.

Original languageEnglish (US)
Pages (from-to)2305-2313
Number of pages9
JournalJournal of Immunology
Volume174
Issue number4
DOIs
StatePublished - Feb 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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