IL-9 is Required for TSLP-mediated Allergic Airway Inflammation (64.3)

Abstract Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine important for the initiation and development of Th2-mediated allergic inflammation. In this study, we identified a significant association between IL-9 and TSLP concentration in the serum of infants with atopic dermatitis. Th9 cultures increased IL-9 production in a TSLP dose-dependent manner, parallel with an increase in pSTAT5 binding to Il9, Irf4 and Gata3 loci. Lung-specific transgenic expression of TSLP stimulated IL-9 production in the lung, and anti-IL-9 treatment attenuated TSLP-induced airway inflammation. Using an adoptive transfer model, we observed that TSLP promoted Th9-induced allergic inflammation in an IL-9-dependent manner, with affects directly on T cells. Together, our results demonstrate that TSLP promotes Th9 differentiation, and define a requirement for IL-9 in TSLP-induced allergic inflammation.