Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses

Baohua Zhou, Mark B. Headley, Theingi Aye, Joel Tocker, Michael R. Comeau, Steven F. Ziegler

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Lung-specific thymic stromal lymphopoietin (TSLP) expression is sufficient for the development of an asthma-like chronic airway inflammatory disease. However, the nature of the downstream pathways that regulate disease development are not known. In this study, we used IL-4- and Stat6-deficient mice to establish the role of Th2-type responses downstream of TSLP. IL-4 deficiency greatly reduced, but did not eliminate, TSLP-induced airway hyperresponsiveness, airway inflammation, eosinophilia, and goblet cell metaplasia, while Stat6 deficiency eliminated these asthma-like symptoms. We further demonstrate, using the chronic model of TSLP-mediated airway inflammation, that blockade of both IL-4 and IL-13 responses, through administration of an anti-IL-4Rα mAb, reversed asthma-like symptoms, when given to mice with established disease. Collectively these data provide insight into the pathways engaged in TSLP-driven airway inflammation and demonstrate that simultaneous blockade of IL-4 and IL-13 can reverse established airway disease, suggesting that this may be an effective approach for the therapy of Th2-mediated inflammatory respiratory disease.

Original languageEnglish (US)
Pages (from-to)6557-6562
Number of pages6
JournalJournal of Immunology
Volume181
Issue number9
DOIs
StatePublished - Nov 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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