朗格汉斯细胞与银屑病

朗格汉斯细胞已被确认为树突状细胞的一个亚群 ,可由CD3 4 + 造血干细胞发育而来。银屑病患者表皮朗格汉斯细胞的表型及功能均与正常人的朗格汉斯细胞不同。目前关于朗格汉斯细胞在银屑病发病中作用的研究集中在朗格汉斯细胞是否通过一氧化氮触发了银屑病 ,以及是否促进了银屑病的病程这两方面。针对朗格汉斯细胞在银屑病发生、发展中的作用可以提出治疗银屑病新策略。     

朗格汉斯细胞与银屑病

朗格汉斯细胞已被确认为树突状细胞的一个亚群，可由ＣＤ３４＾＋造血干细胞发育而来。银屑病患者表皮朗格汉斯细胞的表型及功能均与正常人的朗格汉斯细胞不同。目前关于朗格汉斯细胞在银屑病发病中作用的研究集中在朗格汉斯是否过一氧化氮触发了银屑病，以及是否促进了银屑病的病程这两方面。针对朗格汉斯细胞在银屑病发生、发展中的作用可以提出治疗银屑病新策略。     

树突状细胞亚群在特应性皮炎发病机制中的作用研究进展

特应性皮炎（AD）的病理生理学特征是在急性期以Th2细胞免疫应答为主，慢性湿疹期则有Th1细胞参与。AD患者皮肤和血液中有2种树突状细胞，即髓样树突状细胞和浆细胞样树突状细胞。朗格汉斯细胞和炎性表皮树突状细胞表面均有高表达的IgE高亲和力受体，浆细胞样树突状细胞在防御病毒感染中起保护作用。2种树突状细胞在AD的发病中可能起重要作用。     

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。     

树突细胞在特应性皮炎发病中的研究进展

特应性皮炎是一种慢性复发性炎症性皮肤病,具有血清IgE水平升高、Th2型免疫过度反应以及对多种病原微生物易感性增加等特点.研究表明,朗格汉斯细胞和表皮炎症样树突细胞是在特应性皮炎皮损中出现的两种树突细胞.其中表皮炎症样树突细胞是炎症性皮肤病所特有的一种树突细胞,仅在炎症性皮肤中表达,被激活后可释放大量炎症因子和趋化因子,而在皮炎得到成功控制后逐步消失.在特应性皮炎的病理生理机制中,表皮炎症样树突细胞不仅在炎症的持续和发展中起着重要作用,还可能与皮损局部Th2反应向Thl反应漂移有关.     

特应性皮炎与Th17的研究进展

特应性皮炎是一种慢性复发性、炎症性皮肤疾病,病因复杂,涉及环境、基因及免疫之间的相互作用,其中免疫因素为特应性皮炎发病的重要原因之一。Th17作为一个不同于Th1和2的CD4＋T细胞亚群,已经证实,在特应性皮炎发生发展中起重要的作用。Th17通过分泌白介素-17、21、22等细胞因子诱发炎症反应及免疫反应,参与特应性皮炎发病的免疫学机制。通过物理治疗、药物治疗等手段,可以靶向抑制Th17及相关细胞因子,对治疗特应性皮炎有一定疗效。     

特应性皮炎的转录组学研究进展

【摘要】 随着基因芯片技术、RNA测序技术等转录组学技术发展,特应性皮炎（AD）发病中重要的相关影响因素逐渐被揭示,如不同T辅助（Th）细胞的亚型以及其他免疫相关细胞如巨噬细胞、朗格汉斯细胞;在AD的瘙痒及皮肤屏障破坏方面,相关免疫细胞如Th2细胞及角质形成细胞等所释放白细胞介素4、白细胞介素13、聚丝蛋白、兜甲蛋白等活性物质的异常变化起着主要作用。同时,转录组技术已被用于分析患者治疗前后转录谱的变化从而对患者的病情和治疗效果进行评估等。本文总结近年来在AD转录组学方面的研究进展。     

细胞因子与表皮朗格汉斯细胞的成熟和迁移

朗格汉斯细胞是存在于上皮组织中的一种抗原递呈细胞，在人体的防御系统中起着极为重要的作用。朗格汉斯细胞从表皮向引流淋巴结迁移的过程,亦是朗格汉斯细胞成熟的过程。朗格汉斯细胞的迁移和成熟在激发皮肤免疫反应过程中起着重要的作用，是抗原特异性致敏反应过程中必不可少的一步，许多细胞因子在这一过程中发挥着重要的调节作用。     

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.     

朗格汉斯细胞性组织细胞增生症研究进展

朗格汉斯细胞性组织细胞增生症是一种少见的疾病。近来研究发现吸烟、病毒感染及遗传因素与部分患者发病可能密切相关,T细胞在朗格汉斯细胞性组织细胞增生症的发生中起重要作用。该疾病不仅累及皮肤粘膜,而且可累及中枢神经系统、消化系统、肺脏及甲状腺等多个系统器官。单个系统受累时预后较好,多系统受累时则预后不良。对于朗格汉斯细胞性组织细胞增生症的治疗,应根据不同的病情采取适宜的措施。     

Th17 cells: a new therapeutic target in inflammatory dermatoses

Th17 cells, named for their secretion of interleukin-17 (IL-17), are a new class of T-cells involved in a wide range of cutaneous autoimmune and inflammatory conditions. An overactive Th17 cell response in the skin can produce damaging results. There appears to be a partial role for the Th17 axis in the pathogenesis of a range of dermatological diseases including allergic contact dermatitis, atopic dermatitis, psoriasis, and scleroderma. Immunologists have also discovered a unique association between Th17 cells and cutaneous T-cell lymphoma. The Th17 branch has been linked to a number of additional systemic inflammatory diseases with significant cutaneous pathology such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Behcet's disease. Newly developed treatment modalities for neutralizing the Th17 branch of the immune system are proving to be valuable additions to the current therapeutic armamentarium.     

Bacterial colonization,overgrowth, and superinfection in atopic dermatitis

Staphylococcus aureus infection is a major burden for individuals with moderate-to-severe atopic dermatitis and a known inducer of disease exacerbation. This increased susceptibility to staphylococcal infections has been attributed to abnormalities in the innate immune system of atopic dermatitis (AD) skin, including deficits in barrier proteins and lipids, and a muted response in generating antimicrobial peptides, all of which is further impaired by the activation of Th2 and Th22 immune pathways, which characterizes AD. Skewing of the immune response with a reduced Th1:Th2 ratio and increased adherence of bacteria to AD skin are also thought to contribute. Bacterial species diversity is reduced with flares, concomitant with increases in S. aureus and sometimes clinical infection, which has recently been linked to the finding that commensal bacteria produce anti–S. aureus factors that contribute to the endogenous response. S. aureus produces several virulence factors affecting the skin barrier and immune system, including promoting Th2 cell activation. Best practices for the management of staphylococcal infections include systemic antibiotics, initiation of antiseptics (particularly dilute bleach baths), and sometimes periodic intranasal mupirocin. Newer evidence suggests the possibility that treatment of the skin with commensal bacterial species could also reduce S. aureus growth and increase diversity.     

Effect of an antiallergic drug (Olopatadine hydrochloride) on TARC/CCL17 and MDC/CCL22 production by PBMCs from patients with atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) and monocyte-derived chemokine (MDC/CCL22) are Th2-type cytokines, and it has been reported that serum CCL17 and CCL22 levels are associated with AD disease activity. Olopatadine hydrochloride (Olopatadine) is an antiallergic drug with selective histamine H(1) receptor antagonist activity. The effect of Olopatadine on chemokine production by peripheral blood mononuclear cells (PBMCs) in AD patients has not been completely elucidated. OBJECTIVES: This study was undertaken to clarify the effects of Olopatadine on CCL17 and CCL22 production by PBMCs from patients with AD during the treatment. METHODS: We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks. We also examined disease activity using SCORAD index, eosinophil numbers in peripheral blood and serum levels of LDH. PBMCs from the patients were taken before and after the treatment and cultured with or without dust mite allergen extract (DME) for 3 or 5 days. CCL17, CCL22, IFNgamma, IL-12 and IL-18 levels in the supernatants of cultured PBMCs were measured. RESULTS: SCORAD index and eosinophil numbers in peripheral blood significantly decreased during treatment of AD patients with oral Olopatadine and topical corticosteroids for 4 weeks. The plasma levels of CCL17 and CCL22 significantly decreased after the treatment compared with before the treatment (p<0.05) and were significantly correlated with SCORAD index. PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, showed significantly lower levels of CCL17 production than those taken before the treatment (p=0.018). PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, also showed significantly lower levels of IFNgamma production than those taken before the treatment (p=0.012). CONCLUSION: Our data demonstrate that Olopatadine inhibits CCL17 and CCL22 production by PBMCs from AD patients, which are important regulators of Th2 recruitment in the skin.     

上皮源性细胞因子白细胞介素33、白细胞介素25和胸腺基质淋巴细胞生成素在特应性皮炎发病机制中的作用

【摘要】 表皮屏障功能缺陷及免疫改变是特应性皮炎（AD）发生发展的主要病理生理改变,而皮肤角质形成细胞在各种损伤因素作用下可释放多种炎症因子和介质,其中3种上皮源性因子白细胞介素33、白细胞介素25、胸腺基质淋巴细胞生成素被认为是皮肤或黏膜屏障Th2型免疫应答的有效诱导因子,能够激活免疫细胞,引起Th2型细胞因子分泌,增强Th2型免疫应答,参与AD的发生与发展。本文就3种上皮源性细胞因子在AD发病机制中的作用进展进行总结。     

Thymus- and activation-regulated chemokine (TARC/CCL17) induces a Th2-dominated inflammatory reaction on intradermal injection in mice

TARC/CCL17 (thymus- and activation-regulated chemokine) is a CC chemokine, which binds to the CC chemokine receptor-4 (CCR4) known to be distinctively expressed on Th2 lymphocytes. In atopic dermatitis (AD), the skin is invaded by Th2 lymphocytes in the acute phase. TARC/CCL17 is produced by the keratinocytes in AD lesions, and CCR4 is overexpressed on CLA+ (cutaneous lymphocyte-associated antigen) lymphocytes in the skin and blood. We, therefore, hypothesized that TARC/CCL17 is pivotal in mediating a Th2-dominated inflammation in the skin. To examine this, we injected BALB/c mice with murine TARC/CCL17 in concentrations ranging from 0.1 microg/ml to 10 microg/ml and examined the skin after 48 h. This revealed that TARC/CCL17 induces lymphocytic infiltration of the skin by CD4+ lymphocytes in a dose-dependent manner with a maximum response at 1 microg/ml. Additionally, TARC/CCL17 induced interleukin-4 mRNA but not interferon-gamma mRNA expression in the skin, suggesting that the lymphocytes invading the skin are Th2 cells. Additionally, TARC/CCL17 induced its own production in the keratinocytes along with cutaneous T-cell-attracting chemokine (CTACK/CCL27) mRNA. We, therefore, conclude that TARC/CCL17 induces a Th2-dominated inflammatory reaction when injected into the skin.     

Suppression of IL-17A-induced CCL20 production by cytokine inducible SH2-containing protein 1 in epidermal keratinocytes

BackgroundLesions of atopic dermatitis have fewer Th17 cells than those of psoriasis, resulting in frequent skin infections. Expression of CCL20, a chemokine that is important for recruiting Th17 cells, is suppressed in the lesions of atopic dermatitis. We previously reported that IL-4 induces the expression of cytokine-inducible SH2-containing protein 1 (CIS1), a member of the CIS/SOCS family, in epidermal keratinocytes.ObjectiveTo investigate whether CIS1 influences CCL20 production in epidermal keratinocytes.MethodsExpression of CIS1 was examined in atopic dermatitis skin and in cultured keratinocytes. The effects of overexpression of CIS1 on CCL20 production by IL-17A, and on signaling pathways inhibited by CIS1, were assessed in vitro.ResultsExpression of CIS1 was enhanced in the basal layer of the lesional epidermis of skin with atopic dermatitis. When CIS1 was expressed in keratinocytes using adenoviral vectors, IL-17A-induced CCL20 expression, but not HBD2 or S100A7 expression, was significantly suppressed. TNF-α/IL-1-induced CCL20 production was not altered by CIS1. Overexpression of CIS1 attenuated IL-17A-induced ERK phosphorylation. ERK phosphorylation was mediated by the Act1 and Src family kinase pathways. CIS1 overexpression suppressed Src phosphorylation. Among the Src family kinases, the Yes kinase may have an important role because knockdown of Yes in epidermal keratinocytes resulted in suppression of ERK phosphorylation and CCL20 mRNA expression by IL-17A.ConclusionCIS1 induced by Th2 cytokines has the ability to change the response of epidermal keratinocytes to IL-17A by suppression of Src family kinases.     

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.