A promising therapeutic target for psoriasis: Neuropeptides in human skin

Highlights

• Neuropeptides can interact with the immune system to play the role of neurogenic inflammation.

• Neuropeptide can interact with epidermis to promote keratinocyte proliferation.

• Neuropeptides may exacerbate the development of psoriasis under long-term chronic stress.

Abstract

Psoriasis is a chronic inflammatory skin disease featured by excessive proliferation of keratinocytes, clearly defined round erythema and dry, scaly plaques, long-term inflammatory cells infiltration in skin lesions. However, the physiopathological mechanism of psoriasis is still not clearly understood. Neuropeptides, a class of peptides secreted by the nervous system, may play important roles in promoting excessive proliferation of keratinocyte, enhancing angiogenesis, vasodilation, plasma extravasation and chemotaxis of inflammatory cells during the development of psoriasis. To understand the pathogenesis of neuropeptides in psoriasis, we summarized the function of several common neuropeptides in psoriasis and hypothesize neuropeptides may serve as therapeutic potential novel targets in psoriasis.

Introduction

Psoriasis is a chronic inflammatory skin disease with an incidence of 2–3% of the total population worldwide [1]. It is mainly characterized by an abnormal excessive and rapid proliferation of keratinocytes, vascular proliferation and scaly erythema [2], [3]. The pathogenesis of psoriasis is still not fully understood and may be related to both genetics and environment [4], [5]. Studies have shown that long-term infiltration of inflammatory cells including Th17 and neutrophils, increased plasm IL-17 and IL-23 levels were observed in the psoriatic skin lesions of patients [6], [7], [8]. Available effective therapies for psoriasis are relatively limited. Common accepted treatments include the usage of vitamin D3 derivatives, retinoic acid, corticosteroid and newly developed biological agents. However, the treatment efficacy is poor with frequent recurring of the disease and severe side effects. It has been reported that the use of biological agents to treat psoriasis may lead to cardiovascular disease, serious infections, and new inflammatory bowel disease [9], [10], [11]. Therefore, it is the utmost need to develop new and effective treatments.

The neuropeptides and neurotransmitters released by the cutaneous nerve, including substances P (SP), Calcitonin-related gene (CGRP) and nerve growth factor (NGF), are known to lead to neurogenic inflammation [12]. For instance, during the pathogenesis of psoriasis, certain neuropeptides are involved in (1) promoting keratinocyte proliferation [13], (2) inducing Langerhans cell presenting antigens to Th17 cells, (3) inducing the secretion of IL-17A and IL-6, which will enhance Th17 pathogenic effect on psoriasis [14]. Specific role of each neuropeptide in psoriasis is shown in Fig. 1 and Table 1. Thus, clarifying the links and interactions among the peripheral nervous system, skin, and immune system would help us to better understand the pathogenesis of psoriasis and develop effective therapies for psoriasis [15].