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 signaling 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. Results We demonstrate that IL-21R-deficiency reduces house dust mite-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 to 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.

Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

“…36 Elevated levels are associated with airway inflammation in mouse models and humans. 37–39 The data from the WTC-exposed FDNY cohort is consistent with a Th-2 and Th-17 response predicting airway remodeling and reactivity. These data support further investigation of the innate Th-17 response to pulmonary irritants.…”

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

“…After 10 s, dynamic airway pressure (cm H 2 O × s) was recorded for 5 min. After airway reactivity measurements, serum, BAL fluid, and lungs were collected and processed as previously described (71). …”

T Follicular Helper Cell Subsets and the Associated Cytokine IL-21 in the Pathogenesis and Therapy of Asthma

“…The IL-21 transcript is upregulated in the lung and lungdraining lymph nodes during allergic airway response (12,105). The protein levels of IL-21 and IL-21R are also increased in the pulmonary tissues of asthmatic rats (106).…”