Calcitonin gene-related peptide upregulates IL-17A and IL-22 in γδ-T cells through the paracrine effect of langerhans cells on LC/γδ-T co-culture model

Intense mental stimulation and stress often directly induce or exacerbate psoriasis. On the contrary, patients with nerve injury and nervous system dysfunction have psoriasis remission. The nervous system plays an important role in the inflammatory process of psoriasis, and neuropeptides are considered as local mediators of disease maintenance. To examine the molecular mechanism involved in this, first we analyzed calcitonin gene-related peptide (CGRP)-treated langerhans Cells and γδ-T cells separately. CGRP induced IL-23 mRNA and protein expression via PDK1-Rsk signaling pathway. However, CGRP had no effect on secretion of IL-17A and IL-22 in γδ-T cells. Then we treated LCs/γδ-T cells Co-culture Model with CGRP. CGRP upregulated IL-17A and IL-22 expression in co-culture model through the paracrine effect of LCs. IL-17A and IL-22 are key cytokines of psoriasis. These findings provide a potential mechanism by which nerve factors affect the development of psoriasis.