The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) play pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis. However, the mechanism by which the expression of these innate cytokines is regulated remains unclear. Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. We hypothesized that ITLN is required for allergen-induced IL-25, IL-33 and TSLP expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness. Itln knockdown also inhibited house dust mite (HDM)-induced early upregulation of Il-25, Il-33, and Tslp in a model solely inducing airway sensitization. Using human airway epithelial cells, we demonstrated that HDM-induced increases in ITLN led to phosphorylation of EGFR and ERK which were required for induction of IL-25, IL-33, and TSLP expression. In two atopic dermatitis models, Itln knockdown suppressed expression of Il-33, Tslp and Th2 cytokines and eosinophilic inflammation. In humans, ITLN1 expression was significantly increased in asthmatic airways and in lesional skin of atopic dermatitis. We conclude that intelectin contributes to allergen-induced Il-25, Il-33 and Tslp expression in asthma and atopic dermatitis.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use

Epithelial and plasma miR-181b-5p are potential biomarkers for airway eosinophilia in asthma. MiR-181b-5p may participate in eosinophilic airway inflammation by regulating proinflammatory cytokines expression via targeting SPP1.