Human basophils are a source+ of - and are differentially activated by - IL-31

Background Basophils are important effector cells involved in the pathogenesis of inflammatory skin diseases including chronic urticaria which is associated by increased IL-31 serum levels. So far the effects of IL-31 on human basophils are unknown. Objective To analyse the functional role of IL-31 in basophil biology. Methods IL-31 expression was evaluated in skin samples derived from chronic spontaneous urticaria patients. Oncostatin M receptor (OSMR), IL-31 receptor A (RA) and IL-31 protein expressions were analysed on human basophils from healthy donors. Basophil responses to IL-31 were assessed for chemotaxis, externalization of CD63 and CD203c as well as the release of histamine, IL-4 and IL-13. Results IL-31RA and OSMR were expressed on human basophils. IL-31 was strongly expressed in the skin of patients with chronic spontaneous urticaria and was released from isolated basophils following either anti-IgE, IL-3 or fMLP stimulation. IL-31 induced chemotaxis and the release of IL-4 and IL-13 which was specifically inhibited by anti-IL-31RA and anti-OSMR. Conversely, IL-31 had no effect on CD63 and CD203c externalization or histamine release. Conclusions and Clinical Relevance Human basophils are a source of -and are activated by -IL-31 with the release of pro-inflammatory cytokines and the induction of chemotaxis indicating an important novel function of IL-31 in basophil biology.