| BackgroundVitiligo is a chronic skin disorder, characterized by progressive skin depigmentation because of the loss of melanocytes. An important aspect of vitiligo is the psychological effect ofthe disease. Vitiligo is often immediately visible to others andthose with the condition may suffer social and emotional consequences including low self-esteem, social anxiety, depres-sion, stigmatization and, in extreme cases, rejection by thosearound them In people with a pale white skin colour, vitiligo may cause little concern.According to theGuideline for the diagnosis and management ofvitiligo,the Grades of recommendation/levels of evidence are give 1. Classification: the segmental type and non segmental type. Non segmental type:(1) limited type: limited to a certain parts of the skin or mucous membrane, lesion area<1%. (2) spread in type:scattered, multiple white spot, involving multiple parts, lesion area< 50%. (3) generic hairstyle:type in development, mutual fusion into irregular large white spot, only remaining small islands of normal color of skin. The lesion area> 50%. (4) acromegaly:early vitiligo in acromegaly, sometimes involving the mucous membrane. Segmental type:white spot for one or several pieces, along the skin ganglion, often for unila-teral; 2.Levels of evidence:according to the Vitiligo Disease Activity (VIDA) Scor On a 6-point scale,the patient’s opinion of the present disease activity were devide:if the disease active in the past 6 week,the score will be +4; if the disease active in the past 3 mo nth, the score will be+3; if the disease active in the past 6 month,the score will be+2; if the disease active in the past 1 year,the score will be+1; if the disease stable in the past 1 year,the score will be+1; if the disease stable for at least 1 year and spontaneous repigm-enting,the score will be-1. And acpresent tive refers to expansion of exising lesions or apperance of new lesi-ons;stable condition when symptoms are not present.Consists of scoring of pantients own opionon of the disease activity within the times indicated in the first column.. Wood’s light may be of use in the diagnosis of vitiligoand in the demonstration of the extent and activity of the disease in subjects with skin types I and II. Wood’s light can beof use in monitoring response to therapy.In ICPP (International Pigment Cell Conference)hold by 2011,the Conference on vitiligo branchExperts have proposed vitiligo can be roughly dividedinto two categories:segmental vitiligo and non segmental vitiligo, segmental vitiligo is apart from the other types of vitiligo and because of its special clinical manifestations and pathogenesis.The vitiligo we usually mentionedalways means non-segmental vitiligo. Its pathogenesis is complexand contains many factors, such as genetic factors, oxidative stress, immune factors and mental nerve factors. Howrever The destruction of melanocytes by autoimmune mecha-nism is the major hypothesis towardexplaining the pathogenesis of NSV, and immune-mediated melanoc-yte impaired has been the hot topics in the study of vitiligo. Recent studies show that cell immunity and humoral immunity as well as cytokines are is closely related with the occurrence of vitiligo especially non-segmental vitiligo.A lot of syudies shows thatvitiligo always accompany other autoimmune diseases, suggests a possible link between vitiligo and autoimmune disorders.Thl7 cells were a unique Th cell line.found in recent years that different fromneither Thl nor Th2.Secreting IL-17 is the main characteristicsof Th17, IL-17 can attract other former inflammation factors and chemokines to leads to inflammation,Also IL-17 can work with a variety of cytokines, such as local inflammation medium beta, IL-6, IL-1 TNF to amplify in-flammatory effect.The imbalance of Th17 cells in immune system can mediated inflammatory and autoimmune diseases.Studies have shown that Th17 cells could have the following several mechanisms involved in the pathogenesis of vitiligo:1. The Thl7 cells cytokines directly impact on me-lanocyte Thl7 cells stimulate the cutin cells release mainly cytokines such as IL-17, IL-6 and TNF-a,which is the mainly mechanism of action of vitiligo.IL-17 itself can amplify local inflammatory response that may further inhibit melanin cell proliferation.Pro inflammatory cytokines IL-1 and TNF-a may alsoinduced melanin cell apoptosisby activating particles enzyme and cytotoxic Tcells and macrophages.Regulatory T cells (Treg) CD4+CD25+Treg cells can inhibit the activity of autoimmune T cells, lowering CD4+ and CD8+T cell immune response, which can maintain the stability of the immune function. On the other hand,Th17 cells inhibits the differentiation and function.In the normal circumstances Thl 7 cells and Treg cells inhibit each other and keep a state of dynamic balance in the body. In patients with vitiligo the regulatory T cells and fun-ction defects, the Thl7 cells increased,and disorder the balance between Thl7 cells and Treg cells,which participates in the pathogenesis of vitiligo.3. Thl7 cells interact with dendritic cells (DC):DC has engulfed function, the DC that presenting antigens in the skin is called langerhans cell (LC).LC plays an important role in the cutaneous immune function, were named as "the sentinel", which can recognize the foreign antigens, and react to the change of microenvironment.Th17 cells involved in the immune responses that DC presenting antigen, LC and dermal DC are also presenting antigen and assist Th17 cells involved in immune responses. DC can also involved in the Thl7 cells differentiation and development, improve the reactivity of Thl7 cells.Studies have also shown its specific mechanism for DC through its produce IL a 23 Th17 cells proliferation and participate in inflammation, eventually leading to the onset of vitiligo.Autophagy is referred to be a cellular degradation pathway that involvescytoplasmic content engulfment, delivery and degradation by thelysosome. At least three different forms terms such as macroautophagy,microautophagy and chaperone-mediated autophagy (CMA)have been identified. Of these forms, macroautophagy has been thebestknown impact upon human diseases, which will be the main focus of our study. In a word, autophagy is tightly up regulated to prevent its unbalanced activation. It can be upregulated in response to extra and intracellular stress and also signals such as starvation, growth factordeprivation, endoplasmic reticulum (ER) stress, accumulationof unfolded proteins as well as pathogen infection. Autophagy now is emerging as a spotlight in trafficking events which activate innate and adaptive immunity. As a central playerin the immunological control of pathogen clearance, it maybe also involve in delivering antigens to major histocompatibility complex (MHC)compartments, and regulate lymphocyte survival and homeostasis.Because of the possible importanceof autophagy in self-renovation for immunity, here we need reviewits immune functions and highlightrt its important role in the pathogenesisof autoimmune disease. It is mentioned that autophagy has three primarily types of contributions to the function of the immune system. (1) Type I Specialized immune processes. Such as, by the process that calledxenophagy, can captured and eliminated pathogens. Which will lead to a pattern recognition receptors capture, and also enhancedMHC presentation of antigens, including auto-antigens in some circumstances. (2) Type Ⅱ:Thegeneric role in cellular homeostasis. This refers to the role of autophagy plays in controlling cellular homeostasis inall of cell types. For example, T cells are more dependenton autophagy whereas Bcells will be less sensitive. (3) Type Ⅲ Isolated ATG functions. This means that gene-specific functioninstead of implementation of the whole autophagy pathway. Forexample, ATG12-ATG5 has been observed in the inhibition of retinic acidinducible gene 1-like receptor (RLR) signaling,and ATG9 has also been implicated in down regulating TBK1.These many presently recognized roles of autophagy in innateand adaptive immunity have been remarkable increasing in complexity. There are complicated feedback loops between theautophagy pathway/proteins and immunity/infl-ammation; theese autophagy proteins function as the induction as well as suppression of the immune and both inflammatoryresponses.Once T cells aepart from the thymus, autophagy will play a important role in their survival and homeostasis. A lot decrease of inperipheral T and B lymphocyte numbers and with no alterations by the numbers of the myeloid lineage cells has been observedin Atg3-knockout, Atg5-knockout and Atg7-knockout mice. Defective clearance of mitochondriaand growth factor withdrawal may be a possible explanations. Beside of this,although autophagic cell death is still an important matter of debate, thereis a report that T cells showing excessive autophagy undergo celldeath with an autophagic component. As whatwe discussed above, UVRAG can activates the BECN1-PIK3C3complex, whichi pro mot the level of autophagy. A small nonsegmental vitiligocohort study from Korea suggests that athere a possible association betweenUVRAG and disease susceptibility,and a expanding the number of current disease associated autophagygenes. As UV hasa strongly associated with SLE disease occurrence, the association between UVRAG gene polymorphisms andSLE susceptibility will be of the big interest.A large piecesof evidenceshave emerged to support the role of autophagy in many auto-immune disease, such as diabetes mellitus, rheumatoid arthritis, MS and other aut-inflammatory diseases such as vitiligo.Immune disorders is one of the main pathogenic factors of the non segmental vitiligo,Teak Jeoag et al had founded that uv resistance related gene (ultraviolet radiation to hold associated gene, UVRAG) can activate the Belinnl related pathways, improve the level of cell autophagy, and is closely related to the disease of non segmental vitiligo. autophagy can also affect the generation of melanin body through some cell autophagy related proteins, especially membrane formation related proteins involved in autophagy bodysuch as WIPI1, BECN1 and mTOR inhibitors. Study about WIPI1 is very mature, it is human and yeast Atg18 homologous proteins. WIPI1 mainly involved in the extension of mammalian autophagy body membrane process, but the lack of the content will inhibit the normal small eye melanin cell abnormalities and mRNA accumulation of gathered inside the melanin cell,and MITF has an important roal in the development and survival of melain formation. Studies have shown that join autophagy lysosomal inhibitors or autophagy related protein specificityin vitro cultured cutin forming cells can observed that can interfer RNAs cutin formation of melanin body and melanin content increase. After joining autophagy revulsant melanin corpuscles gathered is restrained. The studies above have shown that autophagy can adjust the cutin degradation in the formation of melanin in the cell body which in turn affect the melanin content.In a word, the Thl 7 cell dysfunction and abnormal secretion of cytokines in non segmental vitiligo play an important role in pathogenesis and immune inflammatory lesions, and autophagy is critical to the survival and function of T cells, and cell autophagy is involved in the process of melanin synthesis, so when Th17 cells abnormal expression level, is its function of autophagy also abnormal or not? Whether the Th17 expression level and the level of autophagy of non segmental vitiligo patients was abnormal? whether there is any correlation between Th17 cells immune disorders and cell autophagy level and whether has the interaction between these two?These studies has not been reported in home, the experiment to extract non segmental vitiligo patients and healthy controls peripheral blood, separate the flow cytometry detection of peripheral blood lymphocytes after borrow Th17 cells and its LC3B autophagy related markers, Beclin1, Bcl-2 and expression level of P62, Th17 cells and their preliminary inquiry whether autophagy level anomalies, Th17 cells in the development of the occurrence of non segmental vitiligo research provide new targets.Objective1. Extraction the peripheral bloodof non segmental vitiligo patients and the healthy controls,then separat mononuclear cell of peripheral (PBMC), detect the expression amount of Th17 cells.2. Extraction the peripheral bloodof non segmental vitiligo patients and healthy controls to detect the expression of the protein involved in autophagy of Th17 cells such as Beclin1, LC3B,P62 and Bcl-2.Method1. According to the standard of vitiligo classification and stages, the experimental group is divided into non segmental vitiligo rapid progress and the stable group, set healthy controls at the same time.Each group needs for 20 cases.In strict accordance with the into and exclusion criteria to select the subject and object.Extraction 8 mlresh peripheral blood of experiments by density gradient and centrifugation isolated from human peripheral blood mononuclear cells (PBMC);2. Testing the amount of Th17 cells express in peripheral blood participants lymphocytes percentage of non segmental vitiligo by using flow cytometry;3. Detecting the expression of protein involved in autophagy of Th17 cells likeLC3B, Beclinl, Bcl-2 and P62 by using flow cytometry;4. Statistical method:using SPSS 18.0 software for statistical analysis, all data are used to mean± standard deviation (x±s).Normality test and f test, single factor analysis of variance to P< 0.05 for the difference was statistically significant.Result1. Testing the peripheral blood volume percentage of PBMC Th17 cells expresseion byusing Flow cytometry, the rapid progressperiod of non segmental vitiligo Th17 cells expression capacity and quantity increase compared with stability and healthy controls, difference between groups was statistically significant (P<0.05);2. The expression of protein involved in autophagy LC 3B and Beclinl of Thl7 cells increased in non segmental vitiligo in rapid progress period than stability and healthy control group, and the Bcl-2 proteinof Th17 cells from non segmental vitiligo rapid progress period decrease than stableperiod and healthy control group, in turn, differences between groups was statistically significant (P < 0.05);P62 express has no obvious difference between the three groups (P> 0.05)Disscussion1.The Th17 cell expression level of peripheral blood from up from patients of non segmental vitiligo rapid progress period increase compared with its stability and healthy controls, the abnormal immunity levels Thl7 cellsparticipated in the development of non segmental vitiligo, Thl7 cells immune hyperfunction is segmental vitiligo important pathogenic factors of this disease.2. In the all of autophagy related markers of Th17 cell, Beclinl is the total cell autophagy start switch, and LC3B is a landmark proteins of autophagy bubble formation, they are positively related to the level of autophagy; the protein of Bcl-2 covalent with Beclinl, inhibit the prossess of autophagy, P62 is a autophagy-lysosome related proteins that ubiquitin for receptor substrates, degradation, its amount of expression is associated with autophagy pathway degradation which is normal. The expression of protein involved in autophagy LC 3B and Beclinl of Th17 cells increased in non segmental vitiligo in rapid progress period than stability and healthy control group,showing that the autophagy level of Th17 cell hyperthyroidism, and the expression of P62 is normal, also explain that the autophagylysosome degradation pathway unobstructed, there is no pathway obstruction nor related autophagy protein pseudo rise phenomenon.3. In a word, Th17 cells and their autophagy had a higher level of non segmental vitiligo patients with rapid progress period, Th17 cells is abnormal in the immune and autophagy and may play an important role in the NSV occurrence and development, but the specific mechanism of interaction has yet to be studied indepth. This article from the perspective of autophagy to explore its role in the development of Thl7 cells in vitiligo, provide a new targets to study the role of Th17 cells in development and incidence of vitiligo... |
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