IL-21 receptor signalling partially mediates Th2-mediated allergic airway responses

S. Lajoie, I. Lewkowich, N. S. Herman, A. Sproles, J. T. Pesce, T. A. Wynn, M. J. Grusby, Q. Hamid, M. Wills-Karp

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Interleukin-21 (IL-21) has been implicated in the development of Th2-mediated immune responses; however, the exact role it plays in allergic diseases is not well understood. Objective: To elucidate the contribution of IL-21 receptor signalling to Th2-dependent immune responses in the lung. Methods: We compared allergic airway responses in wild-type BALB/c and Il21r-deficient mice exposed to local airway challenge with house dust mite (HDM). Results: We demonstrate that IL-21R-deficiency reduces HDM-driven airway hyperresponsiveness (AHR) with only partial effects on airway inflammation. Concomitant with the reduction in AHR in Il21r-deficient mice, significant suppression was observed in protein levels of the Th2 cytokines IL-4, and IL-13. In contrast, IL-21R-deficiency was associated with an increase in PBS- and allergen-driven IgE levels, while IgG1 and IgG2a levels were decreased. Moreover, our results suggest that IL-21 may contribute to AHR through its ability to both directly induce Th2 cell survival and to impair regulatory T-cell suppression of Th2 cytokine production. Importantly, we show that IL-21-positive cells are increased in the bronchial mucosa of asthmatics compared with non-asthmatics. Conclusion: These results suggest that IL-21 plays an important role in the allergic diathesis by enhancing Th2 cytokine production through multiple mechanisms including the suppression of Treg inhibitory effects on Th2 cell cytokine production.

Original languageEnglish (US)
Pages (from-to)976-985
Number of pages10
JournalClinical and Experimental Allergy
Volume44
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • Airway hyperresponsiveness
  • Asthma
  • IL-21
  • IL-21R
  • Tregs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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