The pruritogenic mediator endothelin-1 shifts the dendritic cell–T-cell response toward Th17/Th1 polarization

Abstract

Endothelin-1 (ET-1) is associated with skin diseases such as atopic dermatitis (AD) and psoriasis. ET-1 is enhanced in the skin of AD and psoriasis patients. In addition, plasma levels of ET-1 are elevated in AD and psoriasis. Although both AD and psoriasis are T cell–mediated skin diseases, the association between ET-1 and the T-cell immune response has not been clarified. To evaluate the role of ET-1 in inflammatory skin disease, we sought to investigate the effects of ET-1 on the functions of dendritic cells (DCs) and subsequent immune responses. For this purpose, we immunohistochemically confirmed the upregulation of ET-1 in the epidermis of patients with AD or psoriasis. ET-1 directly induced phenotypic maturation of bone marrow-derived DCs (BMDCs). In addition, ET-1 augmented the production of several cytokines and allogeneic stimulatory capacity of BMDCs. Interestingly, ET-1–activated BMDCs primed T cells to produce Th1 and Th17 cytokines, but not Th2 cytokines. These findings indicate that ET-1 polarizes the DC–T-cell response towards Th17/1 differentiation and may augment the persistent course of inflammatory skin diseases.

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from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2k2F4vv