胸腺基质淋巴细胞生成素在特应性皮炎发病机制和治疗中的研究现状

特应性皮炎(AD)是一种慢性和复发性的炎症性皮肤病，以皮肤干燥、瘙痒和复发性湿疹样皮损为特征。AD的发病机制尚不清楚，目前认为可能与遗传易感性、表皮屏障破坏、免疫失调、皮肤微生物平衡的破坏有关。胸腺基质淋巴生成素(TSLP)是一种IL-7样细胞因子，是过敏性炎症的主要启动因子。TSLP激活的树突状细胞通过OX40配体诱导幼稚的CD4⁺T细胞向Th2细胞分化产生IL-4、IL-5、IL-13和TNF-α等细胞因子参与AD的发病。遗传学、实验和临床证据均表明，TSLP-TSLPR途径与AD的发病机制有关。Tezepelumab(AMG-157/MEDI9929)是一种针对循环TSLP的人类单克隆抗体，阻断TSLP-TSLPR通路可能会对AD产生显著的临床影响。本文阐述了TSLP的生物学特性，进一步了解TSLP-TSLPR通路在AD发病机制中的作用，批判性地评估TSLP靶向药物开发的最新进展，以便为TSLP作为药物靶点提供理论依据。     

胸腺基质淋巴细胞生成素在不同皮肤病中的作用机制研究

【摘要】 胸腺基质淋巴细胞生成素（TSLP）是一种与白细胞介素7（IL-7）类似的细胞因子,可以促进多种细胞的分化和增殖,并使其分泌Th2细胞因子,在机体免疫系统中发挥重要作用。近年来发现在许多皮肤病中TSLP的表达水平异常,在部分皮肤病中其水平高低还与疾病严重程度相关,提示TSLP可能是治疗多种皮肤病的潜在靶点。本文综述近年来TSLP在多种皮肤病（包括炎症性疾病、免疫性疾病、遗传性疾病和肿瘤性疾病）发生发展中的研究进展,为临床相关疾病的诊治提供依据和思路。     

肥大细胞与炎症性皮肤病关系的研究进展

肥大细胞参与皮肤病尤其是炎症性皮肤病的病理生理过程。近年来．人们对肥大细胞与炎症性皮肤病的关系更加重视并进行了较为深入的研究。本文就近年来肥大细胞在异位性皮炎、接触性皮炎、荨麻疹、银屑病、“屏幕皮炎”、慢性郁积性皮炎中的作用及可能参与的病理生理机制作一综述。     

TRP通道在炎症性皮肤病中的作用

瞬时受体电位(TRP)通道是一类非特异性阳离子通道蛋白家族，在皮肤感觉神经元和非神经元细胞中广泛表达，能被多种刺激激活，参与炎症性皮肤病的发生发展。本文重点对TRP通道的不同亚型在玫瑰痤疮、特应性皮炎、银屑病、接触性皮炎等炎症性皮肤病中的作用进行综述，提示TRP通道有望成为炎症性皮肤病的潜在治疗靶点。     

HIV-1相关炎症性皮肤病研究进展

对于HIV/AIDS,皮肤黏膜损害是提示HIV感染的重要线索,也可反映艾滋病的进程。随着高效抗逆转录病毒治疗推广后,HIV相关的皮肤病变流行情况发生改变,感染性皮肤病变和皮肤肿瘤的发生有所减少,但多数炎症性皮肤病变仍广泛发生,本文将就脂溢性皮炎、特异性皮炎、银屑病、嗜酸性毛囊炎、HIV相关瘙痒性丘疹等H I V直接导致的免疫相关炎症性皮肤病变的研究进展加以综述。     

通过天然免疫系统研究炎症性皮肤病

炎症性皮肤病,特别是慢性炎症性皮肤病是皮肤病学中呈高发病率的一类疾病,在这类疾病中最具代表性的是银屑病、特应性皮炎、痤疮等.     

窄谱中波紫外线治疗皮肤病的作用机制

窄谱中波紫外线为近年来治疗皮肤病应用较为广泛的紫外线，经临床证实对银屑病、白癜风、特应性皮炎、瘙痒症及其他炎症性皮肤病有显著疗效且安全性好。治疗机制可能与其较强的穿透性、抑制免疫系统作用及调节各种细胞因子和炎症介质的平衡等有关。对窄谱中波紫外线治疗上述皮肤病的可能作用机制作一综述。     

系统性接触性皮炎的临床研究进展

【摘要】 系统性接触性皮炎是接触过致敏物的个体再次通过系统吸收方式接触同一变应原或具有交叉反应性变应原后发生的变应性炎症性皮肤病,皮疹表现多样且易被忽略。本文从临床表现、致敏物质、发病机制、诊治等多方面总结系统性接触性皮炎的临床相关进展,以期提高临床诊治水平。     

特应性皮炎病因及发病机制的研究进展

特应性皮炎是一种血清IgE增高、常伴发哮喘和过敏性鼻炎的慢性、复发性、瘙痒性、炎症性皮肤病。其发病机制较为复杂 ,与遗传、环境、免疫和对生理药理介质反应异常等因素有关。对特应性皮炎发病机制的研究 ,进一步明确与其发病机理直接相关的效应细胞及效应分子 ,包括局部细胞因子的释放、辅助T细胞的分化、IgE的多种效应、感染因素以及超抗原等 ,以及深入了解它们在特应性皮炎炎症过程中的作用 ,对改善临床治疗效果有重要意义     

特应性皮炎的治疗进展：新药物、新手段、新模式

【摘要】 特应性皮炎是一种反复发作的炎症性皮肤病,现有的治疗方法虽能缓解症状,但仍存在一定的局限性及不良反应。近年来,随着特应性皮炎关键炎症分子的发现和靶向治疗药物的开发,给临床带来一些新的治疗方法和理念。了解特应性皮炎相关生物制剂、小分子药物、辅助治疗、监测手段和疾病管理模式新进展,有助于临床医生更好地治疗及管理特应性皮炎患者。     

Thymic stromal lymphopoietin regulates eosinophil migration via phosphorylation of l‐plastin in atopic dermatitis

Infiltration of eosinophils in atopic dermatitis (AD), which contains inflammatory molecules and cytokines, recruits more inflammatory cells and causes further skin damage. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that induces the proinflammatory Th2 immune response and plays an important role in allergic disease. In this study, we aimed to identify a novel protein that regulates TSLP in eosinophils to further understand the role of eosinophils in atopic dermatitis. Using a proteomics approach, we identified the TSLP‐inducible protein l ‐plastin and confirmed upregulation of l ‐plastin and p‐l ‐plastin in TSLP‐treated human eosinophilic leukaemic (EoL‐1) cells and in eosinophils from AD patients. Migration assays showed that migration of eosinophils increased when cells were treated with TSLP and when cells were treated with TSLP and an additional cytokine such as interleukin (IL)‐3, IL‐4, IL‐5 or IL‐13, when compared to migration of untreated eosinophils. We also confirmed a positive correlation between phosphorylation of l ‐plastin and an increase in migration of TSLP and cytokine‐treated eosinophils. In addition, phosphorylation of l ‐plastin was sensitive to PKCβII inhibition. Our results suggest that TSLP‐induced phosphorylation of l ‐plastin affects eosinophil migration, which may be mediated by the protein kinase C signalling pathway in atopic dermatitis, thus suggesting p‐l ‐plastin as a potential drug target for eosinophil‐targeted allergy therapy.     

Cannabinoid 1 receptors in keratinocytes attenuate fluorescein isothiocyanate‐induced mouse atopic‐like dermatitis

Atopic dermatitis is a chronic inflammatory disease characterized by an impaired epidermal barrier function combined with a chronic Th2‐type inflammatory response and an intense pruritus. Here, we used an experimental mouse model for Th2‐type contact hypersensitivity (CHS) to fluorescein isothiocyanate (FITC) to investigate the potential role of cannabinoid 1 receptors (CB1) in the pathophysiology of mouse atopic‐like dermatitis. Mice lacking CB1 receptors globally (Cnr1^?/?) or specifically in keratinocytes (KC‐Cnr1^?/?) as well as wild‐type (WT) control mice were sensitized and challenged with FITC. We examined ear swelling responses, transepidermal water loss, Th2‐type skin inflammatory responses and serum IgE levels. Both Cnr1^?/? and KC‐Cnr1^?/? showed enhanced CHS responses to FITC and a delayed epidermal barrier repair when compared with WT mice. mRNA levels for IL‐4, thymic stromal lymphopoietin (TSLP) and CCL8, as well as eosinophil activity, were significantly increased in inflamed ear tissue of FITC‐challenged Cnr1^?/? and KC‐Cnr1^?/? mice. Importantly, CB1 receptor‐deficient keratinocytes secreted increased levels of TSLP, a proinflammatory mediator that drives Th2‐type skin inflammation in atopic dermatitis, under basal and Th2‐type inflammatory conditions. Taken together, our results demonstrate that CB1 receptors in keratinocytes help to maintain epidermal barrier homoeostasis and attenuate Th2‐type allergic inflammatory responses. Based on our work, we propose that enhanced epidermal allergen penetrance cooperates with increased production of TSLP and CCL8 by epidermal keratinocytes for the induction of type 2 CD4+ T helper cells. Our results place keratinocytes at the cross‐roads of outside‐in and inside‐out pathophysiologic mechanisms of atopic dermatitis.     

Osthole attenuates mouse atopic dermatitis by inhibiting thymic stromal lymphopoietin production from keratinocytes

Atopic dermatitis is one of the most common skin diseases. Dysregulation of immune system and chronic inflammation were believed to be associated with atopic dermatitis. Osthole was reported to play important roles in antitumor and anti‐inflammation. However, whether osthole has effects on atopic dermatitis remains unclear. In this present study, we explored the biological role of osthole in atopic dermatitis and the molecular mechanism. Atopic dermatitis was induced by 2,4‐dinitrochlorobenzene. Pathological damage of ear was detected by H&E staining. IgE level in serum or thymic stromal lymphopoietin (TSLP) level in supernatant was detected by ELISA. Interleukin (IL)‐4 expression and IL‐13 expression in CD4⁺ T cells were detected using flow cytometry. The expression levels of mRNA or protein levels were detected by RT‐PCR or Western blot. Osthole attenuated atopic dermatitis development in mouse model. Osthole inhibits Th2 cell response, but have on influence on Th1 or Th17 cell response in the skin. In mouse model, osthole treatment significantly inhibited atopic dermatitis via directly inhibiting TLSP expression levels in keratinocytes. Osthole treatment alleviates atopic dermatitis through directly down‐regulating TSLP production from keratinocytes. Osthole may serve as a potential choice for atopic dermatitis treatment in clinic.     

趋化因子CCL27在常见炎陛皮肤病中的作用

临床常见的炎性皮肤病,如,银屑病、特应性皮炎和接触性皮炎等,其典型特征是T淋巴细胞浸润为主的皮肤炎症。趋化因子CCL27主要由皮肤角质形成细胞产生,其惟一受体是CCRl0。CCL27和CCRl0的相互作用,诱导皮肤记忆T细胞向局部皮肤的聚集,形成并维持了各种炎性皮损,因而已成为药物研究的新靶点。尽管目前尚无真正的临床药物可用,但体外研究和动物实验的良好效果为炎性皮肤病的治疗开启了一扇新的大门。     

Pimecrolimus 1% cream (Elidel) for atopic dermatitis

Pimecrolimus is an immunomodulating medication that inhibits production of inflammatory cytokines in the skin and this compound was specifically developed for the treatment of inflammatory skin diseases. Phase II and III clinical trials with the topical formulation of pimecrolimus (Elidel cream, Novartis) have shown that it is safe and effective for use in patients with atopic dermatitis (AD). The US FDA recently approved Elidel for use in patients >or=2 years of age and older with mild to moderate atopic dermatitis (AD).     

Immunologie des allergischen Kontaktekzems

Eczema is one of the most common skin diseases in dermatological practice. The broad medical definition of eczema includes any acute but non-infectious inflammatory reaction of the skin. The relative homogeneity of both the clinical and histological manifestations of eczema is in stark contrast to the profound pathogenetic differences of its various forms. The group of contact dermatitis can be divided into two main categories: irritant and allergic. Irritant contact dermatitis is due to a principally non- immunological inflammatory reaction of the skin to various physical or chemical irritants. In sharp contrast, allergic contact dermatitis is an antigen-specific cellular immune response of the skin, which in general requires prior antigen-recognition and priming of immune cells. A comprehensive understanding of the complex interactions between immune cells, inflammatory mediators and adhesion molecules in the underlying pathogenesis of allergic contact dermatitis is key for a better functional understanding and the development of new therapeutic strategies.