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