KEYWORDS
Yinxieling, Psoriasis, Langerhans cells, Migration, Maturation, Antigen presentation
INTRODUCTION
Psoriasis is a common chronic skin inflammation. The condition is complex and stubborn, prone to recurrent attacks. The main clinical manifestations are erythema, scaly and epidermal thickening, which can take place throughout the body. At present, the incidence of psoriasis in the world is about 2%-3%[1]. In 2014, the organisation passed a resolution recognising psoriasis as a “chronic, non-communicable, painful, disFIGUREuring, and disabling disease for which there is no cure”[2]. Beyond skin inflammation, psoriasis is thought to be as a unique autoimmune and auto inflammatory disease[3]. The immune response is mainly expressed in cytokines: type 1 (Th1) and type 17 (Th17) T cells are activated by IL-12 and IL-23 secreted by dendritic cells(DCs) in the skin[4]. Through various cytokines cause a chronic inflammatory state and alter epidermal hyperproliferation, differentiation, apoptosis, and neoangiogenesis that produce the cutaneous findings seen in this disease[5]. Therefore, DCs play an important role in the pathogenesis of psoriasis.
In general, most DCs are in an immature state and express low levels of co-stimulators and adhesion factors. Immature DCs has strong antigen phagocytosis ability, and will differentiate into mature DCs when taking up antigen or stimulated by certain factors. In this process, DCs migrate from the antigen-exposed peripheral tissues into secondary lymphoid organs, stimulating T cells to launch an immune response[6]. Langerhans cells (LC) are a subpopulation of dendritic cells in the process of differentiation and development, scattered in the basal layer and the spinous layer. It can capture and process antigens invading the skin and deliver them to T cells, stimulating the proliferation and activation of specific T cells. The isolation and identification of Langerhans cells were determined by the expression of HLA-DR, CD1a and Langerin (CD207)[7].
At steady state, the LC of the epidermis constantly probes the environment for invading pathogens by expanding and contracting its dendrites[8, 9]. In an inflammatory state, keratinocytes locally produce proinflammatory cytokines that promote LC maturation and movement to lymph nodes within 3-4 days after these antigenic stimulation and changes in the cytokine microenvironment[10, 11]. LC dissociates from neighboring cells by down-regulating E-cadherin and up-regulatingα 6-integrin, which enters the dermis of the skin through the basement membrane.
Once in the dermis, LC up-regulation the chemokine receptor CCR7,which can access the dermal lymphatic vessels, then enter dermal lymphatic vessels in a CCR7-dependent manner, and finally enter the T-cell region of lymph nodes and initiate adaptive immune responses[12-14]. Dermal LC are regarded as responsible for activating both the Th1 and Th17 infiltrate by secreting IL-12 and IL-23, respectively. This mixed cellular response secretes cytokines and leads to a cascade of events involving keratinocytes, fibroblasts, endothelial cells, and neutrophils that create the cutaneous lesions seen in psoriasis[15].
Owing to the characteristics of multi-component and multi-target, traditional Chinese medicine has more prominent advantages in the treatment of psoriasis, and there are many kinds of traditional Chinese medicine prescriptions put into clinical use. Herbal medicine formulaYinxieling (YXL) is optimized and condensed from the empirical prescription of Guowei Xuan, an national famous old herbalist doctor. The whole prescription is composed of ten herbs. It has the effects of nourishing blood and moistening dryness, cooling blood and detoxifying, removing blood stasis and dredging collateral, and has been used for psoriasis vulgaris more than twenty years in Guangdong provincial hospital[16]. Previous studies have demonstrated that YXL affects psoriasis microenvironment by regulating macrophage polarization by affecting NF-κ B, STAT1 and STAT6 signaling pathways[17]. It can further alleviate psoriasis by inhibiting the phosphorylation of PI3K/Akt/mTOR pathway and affecting the immune response of NK cells in patients with psoriasis[18, 19].
Based on the clinical efficacy of Herbal Medicine formula Yinxieling (YXL), this study aims to investigate its effect on psoriasis-like C57BL/6 mice. Langerhans cells (LCs) play an important role in the occurrence and development of psoriasis. So we also explore the mechanism of YXL on the differentiation and functions of LCs in psoriasis-like mice. So as to provide experimental basis for better treatment of psoriasis with traditional herbal medicine
MATERIALS AND METHODS