A promising therapeutic target for psoriasis: Neuropeptides in human skin
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].
Section snippets
Neuropeptides
Neuropeptides regulate various physiological functions including learning, memory, sleep disorders, and pain [16], [17]. For instance, calcitonin-related gene peptides and neuropeptide S in the amygdala play critical roles in the conduction of chronic pain [17]. Neuropeptide Y and Y5 receptors involve in the suppression of long-term anxiety by the basolateral amygdala [18]. These neuropeptides are characterized by low content and high activity, and widely distribute in various systems of the
Substance P
The tachykinin family (TK) involves a class of neuropeptides, mainly including substance P (SP), neuropeptide A, neuropeptide B, and neuropeptide K, which are derived from pre-tachykinins A and B. Synthetic TK can be stored alone or together with classic transmitters in vesicles and released under specific stimuli or nerve impulses. SP in the TK family has functions on pain conduction, striatum-dopaminergic nervous system activation, immune responses, and digestive activities [27], [28].
Discussion
In recent years, accumulating studies reported the role of the nervous system in chronic inflammatory diseases. The nervous system affects the function of inflammatory cells and keratinocyte by secreting neuropeptides and neurotransmitters. The epidermis affects the function of the nervous system and inflammatory cells through the secretion of NGF and different cytokines. Under normal physiological conditions, nervous system and immune system are harmonious and unified to maintain the stability
Conclusion
Accumulating evidence suggests that alterations in neuropeptides may serve as biomarkers of psoriasis, and provides theoretical basis for potential novel drug development in psoriasis.
Declaration of Competing Interest
The authors declare no conflict of interest.
Acknowledgments
This work was supported by the New Xiangya Talent Projects, the Third Xiangya Hospital of Central South University (20170309 to JL) and the Science and Health Projects of Hunan Natural Science Foundation (2018JJ6094 to JL).
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The authors contribute equally to this study.