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

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

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Interleukin-4
Inflammation
Interleukin-13
Asthma
Goblet Cells
Metaplasia
Eosinophilia
thymic stromal lymphopoietin
Lung
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Zhou, B., Headley, M. B., Aye, T., Tocker, J., Comeau, M. R., & Ziegler, S. F. (2008). Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses. Journal of Immunology, 181(9), 6557-6562.

Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses. / Zhou, Baohua; Headley, Mark B.; Aye, Theingi; Tocker, Joel; Comeau, Michael R.; Ziegler, Steven F.

In: Journal of Immunology, Vol. 181, No. 9, 01.11.2008, p. 6557-6562.

Research output: Contribution to journalArticle

Zhou, B, Headley, MB, Aye, T, Tocker, J, Comeau, MR & Ziegler, SF 2008, 'Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses', Journal of Immunology, vol. 181, no. 9, pp. 6557-6562.
Zhou, Baohua ; Headley, Mark B. ; Aye, Theingi ; Tocker, Joel ; Comeau, Michael R. ; Ziegler, Steven F. / Reversal of thymic stromal lymphopoietin-induced airway inflammation through inhibition of Th2 responses. In: Journal of Immunology. 2008 ; Vol. 181, No. 9. pp. 6557-6562.
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