Inflammasome-IL-1-Th17 response in allergic lung inflammation

Allergic asthma has increased dramatically in prevalence and severity over the last three decades. Both clinical and experimental data support an important role of Th2 cell response in the allergic response. Recent investigations revealed that airway exposure to allergen in sensitized individuals causes the release of ATP and uric acid, activating the NLRP3 inflammasome complex and cleaving pro-IL-1 beta to mature IL-1 beta through caspase-1. The production of pro-IL-1 beta requires a toll-like receptor (TLR) 4 signal which is provided by the allergen. IL-1 beta creates a pro-inflammatory milieu with the production of IL-6 and chemokines which mobilize neutrophils and enhance Th17 cell differentiation in the lung. Here, we review our results showing that NLRP3 inflammasome activation is required to develop allergic airway inflammation in mice and that IL-17 and IL-22 production by Th17 cells plays a critical role in established asthma. Therefore, inflammasome activation leading to IL-1 beta production contributes to the control of allergic asthma by enhancing Th17 cell differentiation.