银屑病角朊细胞Fas、Ice、Bax及bcl-2基因的表达

凋亡(apoptosis)或程序化细胞死亡(programmedcelldeath)是一种不同于坏死且受基因控制的主动性自我消亡过程。迄今,细胞凋亡系统在银屑病发病机理中的作用国内外尚无定论。我们采用免疫组化及图像分析技术研究促凋亡基因(Fas、Ice、Bax)及抗凋亡基因(bcl-2)在银屑病角朊细胞中的表达,以进一步探讨银屑病的发病机理。一、资料和方法病例:15例银屑病及5例正常成人皮肤取自本科及美容科。组织块均常规石蜡包埋、切片,HE染色并经病理证实。试剂及染色方法:促凋亡基因Fas、Ice、Bax及抗凋亡基因bcl-2之多克隆或单克隆抗体均购自SantaCruz公…     

银屑病患者外周血调节性T细胞的检测

目的 检测不同类型银屑病患者外周血中调节性T细胞（Treg）的水平。方法 用流式细胞仪和单克隆荧光抗体检测20例寻常性银屑病、15例脓疱性银屑病和10例红皮病性银屑病患者外周血中CD4+CD25bright调节性T细胞百分率，对寻常性银屑病患者中的10例进行了CD4+CD25hi-intCD127low/-调节性T细胞百分率的检测。结果 红皮病性银屑病组CD4+CD25bright调节性T细胞比例高于其他组（P < 0.01）；寻常性银屑病患者组CD4+CD25hi-intCD127low/-调节性T细胞在CD4+ T细胞中比例为4.39% ± 0.84%，正常人对照组为3.83% ± 1.68%，两组进行Mann-Whitney U检验，差异无统计学意义（P > 0.05）。结论 CD4+CD25bright调节性T细胞可能与红皮病性银屑病的发病有关。     

调节性B细胞与免疫相关性皮肤病

调节性B细胞是B细胞的一种亚群,主要通过分泌白介素-10、转化生长因子-β等抑制性细胞因子,诱导效应性T细胞凋亡、活化调节性T细胞来调节免疫应答和炎性反应。该文对调节性B细胞的分类、功能、相关功能分子及其在接触性超敏反应、非Ig E介导型食物变态反应性特应性皮炎、系统性红斑狼疮、银屑病、天疱疮等免疫相关性皮肤病中的调节机制进行综述,并探讨调节性B细胞靶向治疗的前景及意义。     

内、外源性凋亡通路在瘢痕疙瘩中的研究进展

瘢痕疙瘩是一种以成纤维细胞异常增殖为主要特征的具有局部浸润行为的良性真皮肿瘤。凋亡作为细胞死亡中的一种方式,是一个细胞发生发展后的归宿。在细胞死亡中,尤其是凋亡,被认为是能够抑制细胞恶性程度和异常生长的一种机制。而且,凋亡通路根据起点不同可分为内、外源性凋亡通路,其在瘢痕疙瘩发病机制与治疗机制的研究中均被涉及。因此,本文主要阐述线粒体和内质网介导的内源性凋亡通路和由死亡受体介导的外源性凋亡通路在瘢痕疙瘩中的研究现状。     

银屑病中调节性T细胞的研究进展

调节性T细胞是一类具有免疫调节功能的细胞群,对于维持机体免疫耐受和免疫应答稳态具有非常重要的作用。银屑病是多基因遗传背景下T细胞介导的免疫性疾病,其确切发病机制仍未阐明。在不同病期银屑病患者的皮损和外周血中,调节性T细胞的数量有显著差异,且有功能的改变。治疗后,随着临床症状的好转和PASI评分的下降,外周血中调节性T细胞的比例上升,抑制效应性T细胞的功能增强。调节性T细胞参与银屑病的发生和发展。     

银屑病外周血CD4+CD25+Foxp3+调节性T细胞的表达

目的: 检测CD4+CD25+Foxp3+调节性T细胞在不同类型银屑病患者中的表达.方法: 应用流式细胞仪检测外周血中CD4+CD25+Foxp3+调节性T细胞的表达.结果: 红皮病型银屑病患者外周血中CD4+CD25+Foxp3+调节性T细胞明显高于其他类型银屑病和正常对照组(P<0.05);斑块状银屑病CD4+CD25+Foxp3+T细胞比例高于点滴状患者(P<0.05);脓疱型银屑病患者中脓疱存在患者调节性T细胞比例明显低于脓疱消退患者(P<0.05).结论: CD4+CD25+Foxp3+调节性T细胞通过抑制效应T细胞在银屑病的病情活动中可能发挥重要作用.     

砷化物抑制银屑病角质形成细胞增殖的研究

银屑病主要表现为角质形成细胞过度增殖及凋亡异常,其中角质形成细胞过度增殖是由于细胞凋亡功能障碍或失调所致,凋亡缺陷在银屑病的发病机制巾发挥着重要作用。研究表明,砷化物可以通过对Fas/Fas配体、端粒和端粒酶的影响以及联合阻断JNK等多种途径诱导角质形成细胞凋亡,从而抑制其过度增殖。因此,砷化物有望成为一种局部治疗银屑病的新型药物。     

程序性坏死调控机制及其在角质形成细胞相关疾病中的研究进展北大核心CSCD

皮肤角质形成细胞（keratinocytes,KC）构成了抵御微生物侵袭的第一道防线,它具有严格的增殖与分化过程,构成了表皮的各个层次。细胞凋亡是一种主动、有序、由基因控制的细胞死亡方式,适度的细胞凋亡在皮肤稳态中起重要作用。与凋亡不同,坏死被认为是不可控制的细胞死亡。     

调节性T淋巴细胞和Th17细胞与银屑病的研究进展

银屑病是一种与T淋巴细胞相关的自身免疫性疾病,新近研究发现,除了与Th1细胞有关外,调节性T淋巴细胞尤其叉头/翅膀状螺旋转录因子诱导表达的调节性T细胞和Th17细胞在银屑病的发病过程中起着非常重要的作用。其中,叉头/翅膀状螺旋转录因子（＋）调节性T细胞平衡免疫抑制和免疫激活的转换在银屑病加重方面起到关键作用,Th17细胞分泌的细胞因子IL-17A、IL-17F、IL-22、IL-23、IL-36及肿瘤坏死因子α等在皮肤疾病发生发展中起到重要的作用。银屑病是由调节性T细胞和Th17细胞等多种免疫细胞和细胞因子共同参与的疾病。     

寻常型银屑病患者外周血CD4~+CD25~+及CD8~+CD25~+细胞的检测

目的研究进展期寻常型银屑病患者外周血CD4+CD25+和CD8+CD25+调节性T细胞的数量变化及其在银屑病免疫病理学发病机制中的作用。方法应用流式细胞术对进展期寻常型银屑病患者外周血CD4+CD25+和CD8+CD25+调节性T细胞进行检测。结果进展期寻常型银屑病外周血CD4+CD25+细胞及CD8+CD25+调节性T细胞数量与正常对照组相比,均显著降低(P<0.05,P<0.005),而CD4+CD25+/CD8+CD25+比值无显著性差异(P>0.05)。结论寻常型银屑病的发病与CD4+CD25+和CD8+CD25+调节性T细胞的同步降低有关,与二者的比值无关。     

TWEAK/Fn14信号在银屑病发病机制中的作用及潜在诊疗策略

银屑病是一种常见的慢性炎症性皮肤病,以角质形成细胞异常增殖与分化为重要特征,并涉及多种炎症因子介导的免疫反应机制.肿瘤坏死因子样细胞凋亡弱诱导剂(tumor necrosis factor-like weak inducer of apoptosis,TWEAK)通过与其受体成纤维细胞生长诱导因子14(fibrobla...     

Interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma in psoriasis

Although recent studies have suggested that a variety of cytokines released by keratinocytes and inflammatory leukocytes could contribute to induction or persistence of the inflammatory processes in psoriasis, it remains unclear how production of these cytokines is regulated in psoriatic patients. To elucidate the biologic relevance of these cytokines to the pathogenesis of psoriasis, we investigated serum levels of interleukin 1 alpha, tumor necrosis factor alpha, and interferon gamma in 21 patients with psoriasis vulgaris, together with 21 healthy controls. The mean serum levels of interleukin 1 alpha and tumor necrosis factor alpha were not significantly different from those in controls, while those of interferon gamma were significantly elevated in the patients with psoriasis. Serum levels of interleukin 1 alpha correlated negatively with clinical disease severity expressed as psoriasis area and severity index score and with duration of psoriasis. In contrast, interferon gamma levels were related, although not significantly, to disease severity. In addition, an inverse correlation was noted between the interleukin 1 alpha levels and interferon gamma levels. These results indicate that interleukin 1 alpha and interferon gamma may be relevant to the induction and perpetuation, respectively, of the inflammatory responses in psoriasis, and that these cytokines, which have similar biologic properties, may strictly regulate one another's production in vivo.     

NB‐UVB irradiation attenuates inflammatory response in psoriasis

Psoriasis is a chronic inflammatory disease characterized by immunological imbalance and vasodilation. Many triggering factors for psoriasis initiate inflammation via the activation of NF‐κB. Narrow‐band ultraviolet B (NB‐UVB) irradiation can be used as a general treatment for psoriasis, although the molecular mechanism has not yet been determined. The aim of this study was to elucidate the potential molecular mechanism of NB‐UVB irradiation therapy on psoriasis. We collected serum samples from patients with psoriasis and healthy control, and detected the expression of inflammatory factors by ELISA. In addition, we established mouse model of psoriasis. After different doses of NB‐UVB irradiation, the proportion of CD4⁺, CD8⁺, and CD11c⁺ cells in mouse spleen was detected by flow cytometry. Meanwhile, the expression of inflammatory factors in the damaged skin of mice was detected by RT‐PCR and Western blot analysis, and mouse serum levels of inflammatory factors were detected by ELISA. Our results showed that NB‐UVB irradiation regulated the expression of inflammatory factors in psoriasis patients. In mice, high‐dose NB‐UVB irradiation effectively eliminated IMQ‐induced psoriasis‐like dermatitis and inhibited the expression of pro‐inflammatory factors. In conclusion, our results indicate that NB‐UVB irradiation could regulate the expression of inflammatory factors and attenuate psoriasis plaques.     

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.     

Expression of p53 in lesions and unaffected skin of patients with plaque-type and guttate psoriasis: a quantitative comparative study

Psoriasis is a common inflammatory and hyperproliferative skin disease characterized by hyperproliferation of keratinocytes. The pathogenesis of psoriasis has yet to be determined. The control of cell growth is a delicately balanced process, regulated by external signals or the internal genetic program of an individual cell. In psoriasis, these processes are disturbed and some candidate genes like p53 are suspected of being involved in the pathogenesis of the disease. The p53 protein is essential for the regulation of cell proliferation. The study was performed on 32 patients with psoriasis (24 plaque type, eight guttate type). Biopsy specimens for immunohistochemical determination of p53 protein expression were collected from both the lesional and the nonlesional skin sites that were not exposed to sun in all of the patients (n = 32). Taking the ultraviolet (UV) exposure of the skin into consideration, a third skin sample was taken from each patient (n = 7) who had lesions on the sun-exposed areas. Immunohistochemical assessment of p53 expression in skin was determined as p53 protein expression per 1000 cells (keratinocytes). The statistical analysis revealed that the expressions of p53 per 1000 cells were higher in non-sun-exposed lesional skin than the non-sun-exposed nonlesional skin, also in plaque-type psoriasis than guttate-type psoriasis (P = 0.000, P = 0.046, P = 0.037, respectively). There was a positive correlation between the p53 expression in non-sun-exposed lesional skin versus expression in sun-exposed lesional skin (cubic centimeters = 0.811, P = 0.027). Our results show a stronger association of elevated p53 expression with chronic rather than acute inflammatory psoriasis. This may indicate a mechanistic difference between plaque-type and guttate psoriasis. Alternatively, this could reflect a chronological course as the disease transitions from an acute to a chronic phase.     

MiR‐744‐3p regulates keratinocyte proliferation and differentiation via targeting KLLN in psoriasis

Psoriasis is a chronic inflammatory disease, and microRNAs have been reported to regulate the pathogenesis of psoriasis. Up‐regulated miR‐744‐3p level was identified to associate with psoriasis while the precise functions of miR‐744‐3p in psoriasis were not well‐elucidated. We first confirmed the up‐regulation of miR‐744‐3p in psoriasis by measuring its expression level in psoriatic samples. We explored the roles of miR‐744‐3p on keratinocytes proliferation and differentiation. We searched the targets of miR‐744‐3p and evaluated the roles of one target, KLLN on keratinocytes proliferation and differentiation. We confirmed the up‐regulation of miR‐744‐3p in psoriatic samples. MiR‐744‐3p promoted keratinocytes proliferation while inhibited differentiation. MiR‐744‐3p targeted KLLN and overexpression of miR‐744‐3p resulted in decreased expression of KLLN. Overexpression of KLLN prevented the effects of miR‐744‐3p on keratinocytes proliferation and differentiation. MiR‐744‐3p regulated the proliferation and differentiation of keratinocytes through targeting KLLN in psoriasis.     

Hepatosplenisches T‐Zell‐Lymphom unter Therapie mit TNF‐α‐inhibierenden Biologics: (k)ein Risiko für Patienten mit Psoriasis?

Tumor necrosis factor (TNF)‐α antagonists have considerably improved the therapeutic approach to chronic inflammatory disorders including psoriasis vulgaris. Recently, some cases of highly aggressive hepatosplenic T‐cell lymphoma (HSTCL) have developed in patients with inflammatory bowel diseases (IBD) being treated with infliximab or adalimumab. Analysis of the published data suggests that the emergence of HSTCL is favored by the combination of purine analogues and infliximab or adalimumab in the therapy of a granulomatous inflammation involving Vδ1⁺γδ T cells. Because psoriasis vulgaris is different from IBD in regard to the type of inflammation, the concomitant therapies used and the tissue‐specific subsets of γδ T cells, the use of infliximab or adali‐mumab in psoriasis may not necessarily be associated with an increase in the risk of HSTCL.     

The expression and function of galectins in skin physiology and pathology

The galectin family comprises β‐galactoside–binding proteins widely expressed in many organisms. There are at least 16 family members, which can be classified into three groups based on their carbohydrate‐recognition domains. Pleiotropic functions of different galectins in physiological and pathological processes through extracellular or intracellular actions have been revealed. In the skin, galectins are expressed in a variety of cells, including keratinocytes, melanocytes, fibroblasts, dendritic cells, lymphocytes, macrophages and endothelial cells. Expression of specific galectins is reported to affect cell status, such as activation or death, and regulate the interaction between different cell types or between cells and the extracellular matrix. In vitro cellular studies, in vivo animal studies and studies of human clinical material have revealed the pathophysiologic roles of galectins in the skin. The pathogenesis of diverse non‐malignant skin disorders, such as atopic dermatitis, psoriasis, contact dermatitis and wound healing, as well as skin cancers, such as melanoma, squamous cell carcinoma, basal cell carcinoma and cutaneous haematologic malignancy can be regulated by different galectins. Revelation of biological roles of galectins in skin may pave the way to future development of galectin‐based therapeutic strategies for skin diseases.