T淋巴细胞与银屑病发病机制的关系

银屑病是一种以角质形成细胞(KC)增生分化异常为主要表现的皮肤病,随着研究的进展,人们逐渐认识到T细胞在银屑病发病中的重要作用,银屑病发病原因在于T淋巴细胞的异常,其中参与银屑病发病的T细胞大致经历3个阶段的变化:T细胞活化;T细胞迁移至病变皮肤;活化T细胞释放细胞因子发挥促增殖功能;整个过程中T细胞可促发了银屑病的细胞及分子生物的链式反应加重银屑病皮损.文中总结了这几阶段发生发展的过程,以供参考.     

自噬在银屑病角质形成细胞中的水平及病理意义

自噬是真核细胞中普遍存在的现象,自噬水平的异常已被证明与诸多疾病存在关联.研究表明,自噬水平下降与细胞异常增殖、分化及炎症密切相关,而银屑病皮损中存在细胞增殖、分化与免疫调节异常,表明银屑病发病机制与角质形成细胞自噬水平异常可能存在一定的联系.近年来的研究提示,银屑病角质形成细胞中自噬的水平异常可能参与了银屑病病理机制的形成.概述自噬与细胞增殖、分化及炎症的关系、银屑病角质形成细胞的病理状态以及正常角质形成细胞与银屑病角质形成细胞中的自噬的相关研究.     

寻常性银屑病患者外周血及皮损内MicroRNA-31和MicroRNA-1266的表达水平及临床意义

正寻常性银屑病是一种常见的免疫介导的慢性炎症性皮肤病,以角质形成细胞的增殖和分化异常为特点,在全球发病率为2%～3%~([1])。Micro RNA(miRNA)是一种高度保守的内源性非编码RNA,可通过调节角质形成细胞的分化、增殖和细胞因子反应,在银屑病发病过程中起重要作用~([2-3])。近年来的研究发现,miR-31及miR-1266在固有免疫、炎症性皮肤病及恶性肿瘤发生等各种生物学过程中均发挥着重要的调控作用~([4-5])。然而,     

降钙素基因相关肽在皮肤免疫中作用的研究进展

降钙素基因相关肽(CGRP)是一种主要由感觉神经合成的神经肽,是皮肤的重要感觉神经递质。研究证实其在皮肤免疫中发挥重要作用,CGRP可促进皮肤角质形成细胞及血管内皮细胞增殖,分泌多种细胞因子;CGRP可增强朗格汉斯细胞对Th2型免疫反应的提呈作用,调控朗格汉斯细胞的迁移与分化,抑制朗格汉斯细胞向T细胞呈递HIV-1抗原;CGRP可促进局部CD4+T细胞聚集,通过活化CAMP及蛋白激酶A,促进CD4+T分泌IL-4。CGRP导致局部皮肤增厚、血管扩张、炎性细胞浸润等皮肤炎性皮损的形成,在银屑病、特应性皮炎等多种皮肤炎症性疾病的发生中起重要作用。     

白介素-10与银屑病

银屑病是一种常见的红斑丘疹鳞屑性皮肤病,免疫调节异常是其重要的致病机制之一。白介素-10是一种具有多种免疫调节作用的Th2型细胞因子,能够抑制角质形成细胞过度增殖和分化,促进Ⅰ型细胞因子模式向Ⅱ型转变,减少银屑病皮损T细胞浸润。临床试验证实,IL-10具有显著的抗银屑病作用,且无严重毒副作用,有希望成为治疗银屑病的一种新手段。     

角质形成细胞在银屑病发病机制中的研究进展

银屑病的病因不清 ,但角质形成细胞功能改变具有重要作用。本文综述了近几年有关角质形成细胞增殖和分化调节异常、分泌细胞因子和粘附分子的改变及其与T细胞的相互作用等方面在银屑病的发病机制中作用的研究进展。     

角质形成细胞在银屑病发病机制中的研究进展

银屑病的病因不清，但角质形成细胞功能改变具有重要作用。本文综述了近几年有关角质形成细胞增殖和分化调节异常、分泌细胞因子和粘附分子的改变及其与Ｔ细胞的相互作用等方面在银屑病的发病机制中作用的研究进展。     

银屑病发病机制中T细胞作用的进展

银屑病是一种Th1细胞介导的自身免疫性皮肤病,近来的研究表明,其他细胞也参与其发病过程,尤其是树突细胞、内皮细胞、Th17细胞及调节性T细胞等,其中T细胞的活化、增殖及分化是发病的主要环节,银屑病特征性的角质形成细胞增殖和异常分化及炎性细胞浸润是继发于T细胞活化后释放的细胞因子.一些黏附分子(E/P选择素等)及皮肤淋巴细胞相关抗原-P选择素糖蛋白配体-1复合体和皮肤淋巴细胞相关抗原-CD43复合体在银屑病发病中也起着一定的作用.     

微小RNA主导的免疫调节在银屑病发病机制中的研究现状

银屑病是一种慢性皮肤炎症性疾病,以炎症反应、角质形成细胞增殖加速和表皮更替频繁为主要病理特点,其发病机制复杂,由固有免疫、适应性免疫及其相关免疫细胞和细胞因子参与的免疫调节在其中发挥重要作用.微小RNA参与多种生物学过程,包括细胞增殖、分化、凋亡及器官形成和发育等,与机体免疫调节密切相关.微小RNA可能通过对T细胞、角质形成细胞、固有免疫细胞以及细胞因子的调控参与到银屑病发病.     

信号传导与转录激活因子-3与银屑病

信号传导与转录激活因子-3是一种重要的核转录因子,能被白介素-6、表皮生长因子等细胞因子和生长因子激活,参与细胞增殖、存活、转化、迁移等过程.在银屑病皮损中,角质形成细胞中的信号传导与转录激活因子-3几乎都呈激活状态,它能通过调节银屑病相关发病基因和细胞因子的表达,参与角质形成细胞的增殖、分化和存活以及皮损中血管发生,是银屑病发病中重要的信号传导与转录激活因子.     

Resident skin cells in psoriasis: a special look at the pathogenetic functions of keratinocytes

Psoriasis is a chronic inflammatory skin disease characterized by exaggerated keratinocyte proliferation. Current paradigm indicates that psoriasis is driven by T cell–mediated immune responses targeting keratinocytes. However, psoriasis cannot be explained solely on the basis of T-cell activation, and it is likely that intrinsic alterations in epidermal keratinocytes play a very relevant role in disease expression. In particular, keratinocytes may be important in initiating, sustaining, and amplifying the inflammatory responses by expressing molecules involved in T-cell recruitment, retention, and activation. Keratinocytes are also a relevant source of growth factors for angiogenesis. Finally, intrinsic defects in cytokine and growth factor signaling in keratinocytes may be responsible for their aberrant hyperproliferation and differentiation to T cell–derived signals. Other skin resident cells such as fibroblasts, mast cells, and endothelial cells also contribute to psoriasis pathogenesis by expressing molecules involved in T-cell recruitment and activation.     

MicroRNAs在银屑病发病机制中的研究进展

近年来在MicroRNAs（miRNAs）与银屑病的相关研究中发现,其在银屑病的发病机制中扮演了重要角色,包括调控T细胞、细胞因子、固有免疫及调节角质形成细胞增殖分化、皮肤屏障等方面。miRNAs在血清和组织中均可以稳定存在,未来可能成为银屑病诊断、评价疾病严重程度、监测治疗后反应及预后的新的标志物。本文对miRNAs在银屑病发病机制中的研究进展进行了综述。     

细胞因子在银屑病非皮损区成纤维细胞中的表达

目的：探讨成纤维细胞分泌的细胞因子在银屑病发病中的作用。方法：分别取寻常性银屑病患者非皮损区及正常人皮肤的成纤维细胞进行培养，并建立体外皮肤模型。提取其中的成纤维细胞中的RNA用于cDNA微阵列法检测，比较正常人和银屑病患者非皮损区成纤维细胞在细胞因子基因表达水平的差异。结果：在268个细胞因子及其受体相对应的基因中，与正常人组相比，银屑病组的成纤维细胞表达上升的有24个，下降的有3个。结论：银屑病患者非皮损区的成纤维细胞较正常人的成纤维细胞具有更强的促表皮细胞增殖作用，其细胞因子的表达提示银屑病患者非皮损区具有潜在的向银屑病皮损发展演变的可能。     

Biologics for psoriasis: What is new?

Etiology of psoriasis is unclear but environmental, genetic, and immune factors act significant roles in the pathogenesis of this disease. Helper T cells (TH), plasmoid, and dermal dendritic cells play a prominent role in the development of classical psoriatic lesions. Interleukin stimulation is another important process in the pathogenesis of the disease that directly influences keratinocytes and leading to the formation of psoriatic pattern in the skin. Tumor necrosis factor (TNF) α which releases from keratinocytes activates dendritic cells in the early stages of complex pathogenesis of psoriasis. Activated keratinocytes also produce other proinflammatory cytokines (IL‐1b and IL‐6), antimicrobial peptides, and various chemokines. TNF activates dendritic cells that produce IL‐23, leading to TH17 differentiation. TH17 cells secrete IL‐17A, which has been shown to promote psoriatic skin changes. Consequently, after clarification of these main pathological mechanisms, anti‐IL therapies have been accepted as a major treatment for patients with moderate‐to‐severe psoriasis. Here, actual information will be presented about biological agents currently in clinical use or being tested for clinical application for treatment of patients with psoriasis.     

IL-22在银屑病发病机制中的作用

研究显示,白介素22能促进上皮细胞产生异常炎症介质.白介素22是一种重要的细胞因子,主要由Th17细胞产生,参与炎性细胞浸润,细胞增殖,细胞迁移及防御作用等.在银屑病皮损中,白介素22水平升高,其通过与角质形成细胞表面白介素22受体结合,导致细胞因子和炎症介质改变,起到趋化炎性细胞,促角质形成细胞增殖,抑制角质形成细胞分化的作用,是银屑病发病中重要的细胞因子.介绍银屑病皮疹中白介素22促进炎症细胞浸润和角质化细胞增殖的作用,以及银屑病中角质形成细胞活化产物的变化并通过白介素22治疗银屑病的疗效应证实其作用.

Abstract：

Studies have shown that IL-22 could promote epithelial cells to produce abnormal inflammatory mediators.IL-22 is an important cytokine mainly produced by Th17 cells and participates in inflammatory cell infiltration, cell proliferation, migration, defense, and so on.In psoriatic lesions, the expression level of IL-22 is elevated.By binding to its receptor on the surface of keratinocytes, IL-22 can alter the expressions of cytokines and inflammatory mediators, induce the chemotaxis of inflammatory cells, promote the proliferation and inhibit the differentiation of keratinocytes.Therefore, IL-22 is an important cytokine in the pathogenesis of pasoriasis.This paper describes the upregulatory effect of IL-22 on inflammatory cell infiltration and keratinocyte proliferation, alterations in products of activated keratinocytes in psoriasis, as well as the role of IL-22 in the pathogenesis of psoriasis which has been evidenced by the therapeutic effect of IL-22 on psoriasis.     

Tumour necrosis factor-alpha does not influence proliferation and differentiation of healthy and psoriatic keratinocytes in a skin-equivalent model

Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of psoriasis. Its effect on keratinocytes from healthy and psoriatic skin was investigated. The keratinocytes were co-cultured with healthy and psoriatic fibroblasts in skin equivalents and grown in a serum-free medium for 15 days. TNF-alpha was added, or not, on day 12. The expression of differentiation and proliferation markers was investigated with immunohistochemistry. The epidermal growth rate was assessed by the percentage of Ki-67-positive nuclei in the basal layers of the outgrowths, which were all multilayered and orthokeratotic. The expression of the epidermal growth factor receptor, cytokeratin 16, involucrin and filaggrin displayed a hyperproliferative, regenerative pattern. No statistically significant differences in growth rate were found between the groups. These findings indicate a lack of effect of TNF-alpha on proliferation and differentiation in healthy and psoriatic keratinocytes. Further studies are warranted to elucidate the pathophysiological role of TNF-alpha in psoriasis.     

银屑病发病机制中免疫学研究进展

银屑病的发病机制与免疫关系密切,近几年研究倾向于银屑病是Th1/Th17混合途径的免疫性疾病.银屑病的发病中除了有树突细胞、T细胞、角质形成细胞以及Tb1型的细胞因子如白介素12、白介素18等参与外,还有Th17型细胞因子,如白介素23及白介素22等的参与,Th17型免疫反应可能在银屑病发病中起到重要的作用.     

MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2

MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that play important roles in the regulation of gene expression. We previously identified a characteristic miRNA expression profile in psoriasis, distinct from that of healthy skin. One of the most downregulated miRNAs in psoriasis skin was microRNA-125b (miR-125b). In this study, we aimed to identify the potential role(s) of miR-125b in psoriasis pathogenesis. In situ hybridization results showed that the major cell type responsible for decreased miR-125b levels in psoriasis lesions was the keratinocyte. Overexpression of miR-125b in primary human keratinocytes suppressed proliferation and induced the expression of several known differentiation markers. Conversely, inhibition of endogenous miR-125b promoted cell proliferation and delayed differentiation. Fibroblast growth factor receptor 2 (FGFR2) was identified as one of the direct targets for suppression by miR-125b by luciferase reporter assay. The expression of miR-125b and FGFR2 was inversely correlated in both transfected keratinocytes and in psoriatic skin. Knocking down FGFR2 expression by siRNA suppressed keratinocyte proliferation, but did not enhance differentiation. Altogether, our results demonstrate a role for miR-125b in the regulation of keratinocyte proliferation and differentiation, partially through the regulation of FGFR2. Loss of miR-125b in psoriasis skin may contribute to hyperproliferation and aberrant differentiation of keratinocytes.     

Immunopathogenesis of psoriasis: focus on natural killer T cells

Psoriasis is a common inflammatory skin disease triggered by dysregulated immune response and characterized by hyperproliferation and altered differentiation of keratinocytes. Formation of psoriatic lesions is thought to be elicited by the complex cellular and cytokine network arising from the pathogenic interactions between keratinocytes and components of innate and acquired immune system. Natural killer T (NKT) cells are a heterogenous T-cell lineage that has been implicated in the pathogenesis of various autoimmune diseases including psoriasis. Due to the numerous functions of NKT cells that link innate and adaptive immunity, their role in psoriasis is complex and still elusive. We summarize the currently available literature data on this issue and discuss the possible role of NKT cells in the immunopathogenesis of this autoimmune disease.