Signaling pathways in eosinophils that regulate allergic asthma and inflammation (HYP7P.304)

Abstract

Allergic asthma and inflammation is a disease of the airways. The prevalence of allergic responses and asthma are increasing worldwide, but it is still unclear why some predisposed individuals develop disease. Eosinophils and T helper 2 cells (TH2) and eosinophils are critical cellular mediators in asthma. The signal transducer and activator of transcription (STAT)-6 is a crucial mediator of TH2 cytokine responses, acting downstream of interleukin -4 and -13 (IL-4 and IL-13). We have previously shown that eosinophil derived IL-13 plays an important role in the recruitment of T cells to the lung, and subsequent development of allergic asthma. However whether eosinophils respond to TH2 signals to control allergic airway inflammation is unclear. The objective of this study is to understand the role of STAT6 in eosinophil-dependent regulation of allergic asthma and inflammation. Using ΔdblGATA mice lacking eosinophils and transfer of STAT6-/- eosinophils, we found that compared to ΔdblGATA reconstituted with WT eosinophils, eosinophils lacking STAT6 were unable to rescue recruitment of CD4+ T cells and eosinophils into the lungs compared to WT eosinophils. These data indicates that STAT6 is important in the recruitment of both T cells and eosinophils to the lung during the development of allergic airway inflammation. Ultimately, deciphering the mechanisms of intracellular and cytokine signals will afford us improved insights on developing therapeutic strategies in asthma.