特应性皮炎与皮肤微生态的研究进展

特应性皮炎是一种慢性、复发性、炎症性皮肤病.其发病机制复杂,在遗传基础上,表皮屏障功能异常、环境过敏原暴露、金黄色葡萄球菌定植等诱发的免疫炎症反应均参与其发病.皮肤微生态是皮肤表面微生物构成的复杂生态系统,近年研究提示,微生态异常在特应性皮炎的发病过程中起重要作用,特应性皮炎患者的皮肤除了存在金黄色葡萄球菌定植增多外,还存在表皮葡萄球菌等其他微生物数量和功能的改变.因此,进一步揭示各种微生物群落与特应性皮炎发病的关系,有助于特应性皮炎的防治.     

特应性皮炎的体外3D皮肤模型

特应性皮炎是一种慢性炎症性皮肤病,其病理机制涉及表皮屏障功能破坏、皮肤微生物组异常和2型炎症免疫失调之间复杂的相互作用.随着组织工程技术发展,3D皮肤模型已与正常人体皮肤结构接近.通过模拟特应性皮炎的病理机制,许多研究者成功构建出特应性皮炎的3D皮肤模型.该模型被应用于特应性皮炎的病理机制研究、药物筛选方面,是进行特应...     

钙调神经磷酸酶抑制剂治疗特应性皮炎的进展

特应性皮炎(atopicdermatitis,AD)是一种炎症性、免疫介导的皮肤病.     

P物质在特应性皮炎发病机制中的地位

特应性皮炎是一种反复发作的瘙痒性皮肤病 ,病因相当复杂 ,牵涉到遗传、精神、免疫、环境等一系列因素 ,其确切发病机制至今尚不十分清楚。近年来有人提出神经 -内分泌 -皮肤免疫的系统学说 ,试图通过这一学说解释特应性皮炎的发病机制。现就一种神经肽类物质———P物质介入特应性皮炎发病的免疫机制加以综述     

特应性皮炎发病过程及其机制研究现状探讨

特应性皮炎是一种复发性的以严重瘙痒为主要临床表现的慢性过敏性皮肤病。全球特应性皮炎的患病率不断上升,然而其发病机制尚不明确。"Outside to inside"是近几年对于特应性皮炎发病机制阐述较为完善的假说,该假说提示特应性皮炎的发病可能是由皮肤向免疫、由外向内渐进性的过程。     

特应性皮炎与维生素D

特应性皮炎是婴幼儿时期常见的炎症性皮肤病,其发病机制复杂,涉及遗传、环境、免疫以及屏障功能异常。"维生素D假设"理论揭示了高纬度地区过敏性疾病包括特应性皮炎发病率增加的现象。临床研究结果提示维生素D水平与特应性皮炎发生以及疾病严重度相关;补充维生素D能缓解病情。然而目前维生素D与特应性皮炎关系仍然备受争议,其参与特应性皮炎发病的具体机制以及作为特应性皮炎常规治疗手段的地位目前并不明确。     

调节性T细胞在特应性皮炎中的作用

调节性T细胞是一类具有免疫调节作用的T细胞亚群,主要通过细胞间直接接触和间接接触发挥免疫抑制作用,参与机体自身免疫耐受的形成.特应性皮炎是一种常见的慢性复发性炎症性皮肤病,发病机制复杂.对特应性皮炎发病机制的研究主要集中在Th2细胞,最近的研究发现,调节性T细胞在特应性皮炎中发挥了重要作用.研究调节性T细胞在特应性皮炎患者从儿童到成人期的变化,可以更好地探讨其在疾病发病过程中的作用并提示新的治疗方法.     

妊娠与特应性皮炎的相关性

特应性皮炎是一种慢性瘙痒性炎症性皮肤病,患者常具有特应性疾病的家族史。该病不同时期的皮损具有一定的特征性,皮肤干燥是共同特征。特应性皮炎的患病率呈逐年上升趋势,严重影响患者的心身健康。妊娠期内分泌、免疫、代谢等因素的变化,可对特应性皮炎的发生发展产生影响。文中就妊娠对孕妇特应性皮炎病情的影响、妊娠期影响胎儿特应性体质形成的因素、孕妇饮食对其后代发生特应性皮炎的影响及妊娠期特应性皮炎的治疗进行了概述。     

P物质在特应性皮炎发病机制中的地位

特应性皮炎是一种反复发作的瘙痒性皮肤病，病因相当复杂，牵涉到遗传，精神，免疫，环境等一系列因素，其确切发病机制至今尚不十分清楚，近年来有人提出神经－内分泌－皮肤免疫的系统学说，试图通过这一学说解释特应性皮炎的发病机制，现就一种神经肽类物质－P物质介入特应性皮炎发病的免疫机制加以综述。     

中间丝蛋白与特应性皮炎皮肤屏障功能

特应性皮炎的病因复杂,发病机制尚未明确,可能是遗传、环境、皮肤屏障功能缺陷及免疫相互作用的结果.中间丝蛋白基因是表皮分化复合物基因簇的成员之一,与细胞膜形成及表皮终末分化密切相关.中间丝蛋白基因突变是特应性皮炎发病的重要易患因素之一,中间丝蛋白的减少和缺失,可能是引起特应性皮炎等十燥性皮肤病的主要原因.     

固有淋巴样细胞2与特应性皮炎的研究进展

特应性皮炎是一种慢性炎症性疾病,在儿童中多见,且多有哮喘、过敏性鼻炎等疾病的家族史.该病的发病机制尚不明确,与皮肤屏障缺损、遗传易感性、环境危险因素及免疫调节异常等多个因素相关.研究发现,特应性皮炎与固有淋巴样细胞所介导的免疫反应相关,特别是2型固有淋巴样细胞,与该型细胞相关的白介素4、5和13等一系列细胞因子在特应性皮炎的发病过程中发挥重要作用,这一进展可为特应性皮炎提供新的治疗靶点.     

Immunology and Treatment of Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory disease hypothesized to be the product of complex interactions among the host's environment, susceptibility genes, skin barrier dysfunction, and immune system dysregulation. The objective of this article is to describe the pathobiology and treatment of AD, with particular focus on the role of immune system dysregulation and therapies designed to target this. Literature review indicates that there are immunologic differences between the lesional and non-lesional skin of atopic individuals, and that the non-lesional skin of atopic individuals presents an immunologic profile distinct from that of the skin of healthy individuals. Thus, immune system dysregulation is postulated to be a key contributing factor to the complex etiology of AD. Immunomodulatory agents such as topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs), which address the underlying immunopathology of AD, are the foundation for the pharmacologic treatment of flares. TCSs and TCIs both target the inflammatory response responsible for an AD flare but via two distinct mechanisms of action. Whereas TCSs have a more widespread impact on the immune system, the action of TCIs is targeted to the calcineurin pathway and inhibition of T-cell activation. Together, TCSs and TCIs represent the backbone of a long-term treatment strategy for AD.     

Vitamin D receptor activation improves allergen-triggered eczema in mice

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that has increased in prevalence over the last several decades in industrialized countries. AD is a multifactorial, heterogenous disease with a variety of defects in the immune system, in antimicrobial defense mechanisms and epidermal barrier integrity, which collectively contribute to the risk and severity of AD development. Vitamin D receptor (VDR) signaling has been shown to be important not only in the immune system but also in the skin and in particular keratinocytes to regulate skin homeostasis and epidermal barrier function. However, this work aimed to analyze the role and clinical efficiency of VDR activation by a VDR agonist without calcium-mobilizing activity in a mouse model of allergen-triggered eczema. We show that the systemic administration of the low-calcemic VDR agonist significantly improved the allergen-triggered eczema. Thereby, forkhead box P3 (Foxp3)-expressing regulatory T cells, revealed to have a role in AD, were selectively increased in the skin of VDR agonist-treated mice. Moreover, our results demonstrate a marked induction of skin barrier gene and antimicrobial peptide gene expression in skin lesions of VDR agonist-treated mice. Thus, our study provides evidence that systemic VDR agonist treatment may improve allergen-triggered eczema in vivo.     

胶带剥离法在特应性皮炎研究中的应用

特应性皮炎(atopic dermatitis,AD)是一种常见的慢性、复发性、炎症性皮肤病,本病的病因及发病机制尚不明确,屏障缺陷及免疫缺陷在发病中起重要作用。胶带剥离法即通过反复使用合适胶带来依次去除皮肤浅层,由于无创性及可重复性等优点,近年来被应用到AD研究中,发现皮肤浅层中某些物质的RNA、蛋白质、脂质及细胞因子等的异常表达,有助于揭示AD发病机制。本文主要介绍胶带剥离法及其在AD中的具体应用。     

Personalized Immunomodulatory Therapy for Atopic Dermatitis: An Allergist's View

The current standard medical therapy for atopic dermatitis (AD) mainly focuses on symptomatic relief by controlling skin inflammation with topical corticosteroids and/or topical calcineurin inhibitors. However, the clinical efficacy of pharmacological therapy is often disappointing to both patients and physicians. The terminology of AD contains a historical meaning of eczematous dermatitis caused by hypersensitivity reaction to environmental inhalant or food allergen. Complex interrelationships among genetic abnormalities, environmental triggers, skin barrier defects, and immune dysfunction resulting in a vicious domino-circle seem to be involved in the development and maintenance of AD. In the viewpoint of AD as an allergic disease, complete avoidance of clinically relevant allergen or induction of specific immune tolerance through administrations of allergen (allergen immunotherapy) can provide clinical remission by breaking the vicious domino-circle maintaining a chronic disease state. In recent clinical studies, monoclonal antibodies including the anti-interleukin-4 receptor antibody and anti-B cell antibody induced significant clinical improvements in patients with AD. The detailed characteristics of immune dysfunction are heterogeneous among patients with AD. Therefore, a personalized combination of immunomodulatory therapies to reduce hypersensitivity (allergen immunotherapy) and correct immune dysfunction (monoclonal antibody therapy) could be a reasonable therapeutic approach for patients with AD. Future immunomodulatory therapies for AD should be developed to achieve long-term treatment-free clinical remission by induction of immune tolerance.     

β-endorphin modulates lipogenesis in human sebocytes

Proteinase-activated receptors are G-protein-coupled receptors with seven-transmembrane domains activated by serine proteinases. PAR-2 is a receptor for mast cell tryptase, house dust mite allergens, bacterial antigens and trypsin, for example, indicating a role of PAR-2 during inflammation and immune responses. In the skin, PAR-2 is expressed by keratinocytes, endothelial cells, certain immune cells and nerves, suggesting a broad regulatory role of proteases in the skin. Recently, PAR-2 has been demonstrated to be involved in neurogenic inflammation. Therefore, we examined whether neuronal PAR-2 may be involved in pruritus of human skin. The endogenous PAR-2 agonist tryptase was increased up to fourfold in atopic dermatitis (AD) patients. PAR-2 was markedly enhanced on primary afferent nerve fibres in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists provoked enhanced and prolonged itch when applied intralesionally. Interestingly, itch upon mast cell degranulation prevailed despite local antihistamines in AD patients only. Thus, we identified enhanced PAR-2 signalling as a new link between inflammatory and sensory phenomena in AD patients. PAR-2 antagonists, thus, represent a promising therapeutic target for the treatment of cutaneous neurogenic inflammation and pruritus.     

Insight into newly discovered innate immune modulation in atopic dermatitis

Atopic dermatitis (AD) is a highly pruritic, chronic relapsing inflammatory skin disease characterized by innate and adaptive immune reactions. In AD, innate immune mechanisms such as pattern recognition receptors and antimicrobial peptides have been investigated in detail, but recently, epidermis‐derived cytokines, namely thymic stromal lymphopoietin (TSLP), IL‐25 and IL‐33, were shown to participate in innate immune reactions independently of adaptive immunity. In addition to conventional innate cells, such as mast cells, basophils and eosinophils, Th2 cytokine‐producing invariant natural killer T (iNKT) cells, innate lymphoid cells (ILCs) and Th17/Th22 cytokine‐producing innate cells – iNKT cells and natural killer (NK)‐like cells – can participate in innate immune modulation in AD. Accordingly, early control of innate immune responses in AD before activation of adaptive immune responses by conventional T and B cells that perpetuate chronic skin inflammation may adequately alleviate acute exacerbations of AD. Therefore, we hypothesized that select immune modulators targeting the innate immune response could potentially be used for individualized treatment of AD.     

The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition

Atopic dermatitis (AD) is a highly prevalent, chronic inflammatory skin disease that affects children and adults. The pathophysiology of AD is complex and involves skin barrier and immune dysfunction. Many immune cytokine pathways are amplified in AD, including T helper (Th) 2, Th22, Th17 and Th1. Current treatment guidelines recommend topical medications as initial therapy; however, until recently, only two drug classes were available: topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). Several limitations are associated with these agents. TCSs can cause a wide range of adverse effects, including skin atrophy, telangiectasia, rosacea and acne. TCIs can cause burning and stinging, and the prescribing information lists a boxed warning for a theoretical risk of malignancy. Novel medications with new mechanisms of action are necessary to provide better long‐term control of AD. Phosphodiesterase 4 (PDE4) regulates cyclic adenosine monophosphate in cells and has been shown to be involved in the pathophysiology of AD, making it an attractive therapeutic target. Several PDE4 inhibitors are in clinical development for use in the treatment of AD, including crisaborole, which recently became the first topical PDE4 inhibitor approved for treatment of mild to moderate AD. This review will further describe the pathophysiology of AD, explain the possible role of PDE4 in AD and review PDE4 inhibitors currently approved or being investigated for use in AD.     

Modeling atopic dermatitis with increasingly complex mouse models

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder that affects approximately 15% of children in the United States. A complex disorder, AD is characterized by both skin barrier impairment and immunologic abnormalities, including decreased innate immune function and a polarized adaptive immune response. Mouse models have demonstrated the complex interdependence of immune cell-keratinocyte interactions and teased apart gene-environment relationships in a controlled setting. In this issue, Nagelkerken et al. present a mouse model with transgenic expression of apolipoprotein C1 that disrupts the skin lipid barrier and manifests many hallmark features of AD.     

Atopic Dermatitis

Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2-deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information.