Opposing roles of IL‐17A and IL‐25 in the regulation of TSLP production in human nasal epithelial cells

Abstract

The importance of IL-17A, IL-17F, and IL-25 in allergic rhinitis (AR), as well as their possible role in regulation on thymic stromal lymphopoietin (TSLP) production in nasal epithelial cells, is not well understood. To determine the possible regulation of IL-17A, IL-17F, and IL-25 on TSLP production in the initiation of allergic responses. The levels of IL-17A, IL-17F, IL-25, and TSLP in nasal lavages of patients with AR were measured using an enzyme-linked immunosorbent assay (ELISA) and compared with that in normal controls. Then, primary human nasal epithelial cells (HNECs) were stimulated with dsRNA (0-75 microg/ml), as well as IL-17A (100 ng/ml), IL-17F (100 ng/ml), and IL-25(100 ng/ml). The mRNA expression of IL-17A, IL-17F, IL-25, TSLP, as well as the chemokines CCL20, IL-8, and eotaxin was analyzed using quantitative real-time PCR, and their protein levels in the supernatants of cultured HNECs were determined by ELISA. Both TSLP and IL-17 cytokines are significantly elevated in patients with AR. dsRNA was found to increase the production of IL-17F, IL-25, TSLP, CCL20, and IL-8 in HNECs. Furthermore, IL-25 significantly enhanced dsRNA-induced TSLP production in primary HNECs and was dominant to the inhibitory effect of IL-17A on TSLP regulation. Our study provides the first evidence that both IL-17F and IL-25 can be induced by dsRNA in HNECs. Despite of the opposing effects of IL-17A and IL-25 on TSLP regulation in HNECs, IL-25 was dominant to IL-17A, providing a plausible explanation for the simultaneous upregulation of IL-17 cytokines and TSLP in patients with AR.