title: IL-21 receptor signalling partially mediates Th2-mediated allergic airway responses.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins School of Public Health, Baltimore, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lajoie
authors.forename: I
authors.initials: I
authors.lastname: Lewkowich
authors.forename: N S
authors.initials: NS
authors.lastname: Herman
authors.forename: A
authors.initials: A
authors.lastname: Sproles
authors.forename: J T
authors.initials: JT
authors.lastname: Pesce
authors.forename: T A
authors.initials: TA
authors.lastname: Wynn
authors.forename: M J
authors.initials: MJ
authors.lastname: Grusby
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
authors.forename: M
authors.initials: M
authors.lastname: Wills-Karp
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053655:Receptors, Interleukin-21 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000485:Allergens; D016207:Cytokines; D053655:Receptors, Interleukin-21; D007073:Immunoglobulin E
keywords: IL-21; IL-21R; Tregs; airway hyperresponsiveness; asthma