TSLP augments Th9-mediated allergic inflammation (163.23)

Abstract

Abstract Thymic stromal lymphopoietin (TSLP) is an epithelial cell derived cytokine important for the initiation and development of Th2-driven allergic inflammation in asthma and atopic dermatitis. The role of TSLP in Th9-mediated inflammation has not been identified. In this study, we investigated the role of TSLP on Th9 differentiation and IL-9 production both in vitro and in vivo. Our data showed that Th9 cells expressed greater amounts of TSLP receptor than Th2 cells, and addition of TSLP to Th9 cultures increased IL-9 production in vitro. Lung-specific transgenic expression of TSLP stimulated IL-9 production in BALF and lung. To further characterize the role of TSLP on Th9-mediated allergic inflammation in vivo, we transferred OVA-differentiated Th2 or Th9 DO11.10 CD4+ T cells to wild type recipient followed by OVA or OVA+TSLP challenge. Our data showed that challenge with OVA+TSLP, but not with OVA alone increased IL-9 production and allergic inflammation in mice injected with Th9 cells, with less effect on Th2 cells. Therefore, Th9 cells can mediate TSLP-mediated exacerbation of allergic airway inflammation. These results suggest that, while both Th2 and Th9 promote allergic inflammation, Th9 cells along are sufficient to respond to TSLP for increased allergic inflammation. Our findings provide a potential role of TSLP on the development of Th9-mediated allergic inflammation.