IL-22在银屑病发病机制中的研究进展

银屑病作为一种常见的慢性皮肤病,影响了全球2％的人口.时至今日,银屑病的发病机制尚未完全阐明,银屑病的治疗也没有行之有效的方法.IL-22是IL-10细胞因子家族的一员,它通过作用于角质形成细胞在银屑病发生发展中起重要作用.本文综述了IL-22作用于角质形成细胞的作用机制,并对银屑病的治疗方法提出展望.     

整联蛋白信号与银屑病发病分子机制

整联蛋白可激活酪氨酸激酶和维持生长因子的生物活性 ,实现细胞外基质 -整联蛋白 -细胞内的信号转导功能 ,调节细胞生长、分化、粘附等生理功能 ;在病理状态下 ,如银屑病整联蛋白表达异常 ,可介导角质形成细胞的过度增生、异常分化甚至炎症的发生。本文综述调节细胞基本行为的整联蛋白信号转导及其与银屑病分子发病机制的关系     

Th17细胞与角质形成细胞相关细胞因子在银屑病中的作用

银屑病的发病机制主要表现为以T细胞介导的以角质形成细胞（KC）为靶点的免疫应答反应。在T细胞因子作用下,KC可能会出现异常的增殖和分化,其通过表达细胞因子参与T细胞的记忆和活化。Th17细胞是一种新发现的CD4^＋T细胞亚群,因其分泌IL-17（IL-17A）而命名。IL-17促进KC产生VEGF、IL-8、GM．CSF、TNF—α、CXCL10等细胞因子可能会诱发和加重银屑病。     

银屑病患者外周血淋巴细胞亚群的变化

目的 探讨进行期、静止期和退行期的银屑病患者外周血淋巴细胞亚群的变化及免疫机制.方法 本研究评估了77例寻常型银屑病患者(28例进行期、23例静止期、26例退行期)的外周血单个核细胞(PBMCs)各组中各淋巴细胞的比率.结果 与退行期相比,进行期和静止期患者的CD3+、CD4+和CD8+淋巴细胞的百分率均显著升高(P<...     

Tc17细胞在银屑病发病及复发机制中的进展

细胞毒性T细胞17(Tc17)是近年发现的新型CD8+T细胞亚群,与CD8+T细胞的经典亚群Tc1、Tc2细胞显示强烈不同的细胞毒性,Tc17不表达或低表达细胞毒性,以分泌IL-17为主要特征.近年来研究提示银屑病发病机制中有Tc17细胞的重要参与.最近研究还发现Tc17细胞具有记忆细胞表型,作为银屑病组织常驻记忆T细...     

银屑病皮肤病损中免疫细胞及分子的作用

近年来,随着银屑病研究的深入,有关细胞免疫在其发病机理中的研究获得较多的实验资料,特别是活化的T淋巴细胞与角朊细胞之间的相互作用,受到大多数学者的重视。本文就T淋巴细胞参与银屑病发病的证据,皮肤病损中T淋巴细胞的活化,T淋巴细胞亚群以及T淋巴细胞与表皮角朊细胞的相互作用,进行了综述。     

ERK 信号通路介导银屑病角质形成细胞过度增殖的调控机制

银屑病是常见的慢性、 复发性、 炎症性皮肤病, 角质形成细胞 ( keratinocyte, KC) 增殖分化失 调作为其发病原因之一, 具体机制尚未明确。 细胞外信号调节激酶 ( extracellular signal regulated kinase, ERK) 信号通路在其中发挥着重要作用, 微小 RNA (microRNA, miRNA)、 长链非编码 RNA ( lncRNA)、 细胞因子等作为 ERK 信号通路的上游分子参与调控银屑病表皮角质形成细胞的增殖与分化过程。 文章旨在 对这一通路在银屑病角质形成细胞过度增殖中的作用机制做一综述。     

雷公藤多甙对哮喘患者TH1/TH2细胞因子平衡状态的调节作用

目的：探讨雷公藤多甙（GTT）对哮喘患者的抗炎、平喘作用的机理。方法：选择60例过敏性哮喘患者随机分为GTT治疗组和对照组，治疗前后分别采用ELISA法检测PBMC培养液上清液中白细胞介素4（IL－4）、γ干扰素（IFN－γ）、可溶性白细胞介素2受体（sIL－2R）、可溶性IgE低亲和力受体（sCD23)含量，采用逆转录PCR检测IL－4mRNA表达量，采用嗜碱粒细胞脱颗粒试验检测嗜碱粒细胞释放能力（BRA）。结果：哮喘患者上清液中IL－4、sIL-2R、sCD23含量、IL－4mRNA表达量及BRA均显著增高，而IFN－γ含量显著减少。治疗组经GTT治疗后，上清液IL－4、sIL-2R、sCD23含量、IL－4mRNA表达量及BRA均显著降低，而INF－γ含量显著增高。对照组治疗前后上述指标差异均无显著性。结论：GTT能显著抑制哮喘患者T细胞和B细胞的活化，能纠正体内TH1和TH2细胞因子的失衡状态，并能降低BRA。这可能是GTT抗炎、平喘作用的重要机理之一。     

Th17细胞及其相关因子在银屑病发病中的作用及其分子机制

银屑病是一种自身免疫性疾病,表现为以T细胞为主的免疫功能紊乱。Th17细胞是一种能分泌白细胞介素17(IL-17)的T细胞亚群,参与多种自身免疫性疾病的免疫调节。研究发现银屑病患者外周血中存在IL-23和Th17类细胞因子的显著升高,IL-23/Th17细胞轴在银屑病发病机制中有重要作用。除Th17细胞本身,在银屑病患者皮损处,IL-17、IL-22、IL-21等Th17相关细胞因子亦发生改变。调节性B细胞在银屑病的发病过程中有可能通过产生IL-10发挥负向免疫调节功能。本文主要从Th17细胞及其相关因子与银屑病,调节性B细胞和Th17细胞在银屑病发病机制中的拮抗作用几个方面进行综述。     

T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products

Psoriasis vulgaris has been recognized lately as an immunologically mediated inflammatory skin disease. To analyze the pathogenetic role of T lymphocytes in the generation of psoriatic skin lesions, 105 T cell clones (TCC) and 10 T cell lines (TCL) were differentially isolated from dermis and epidermis of psoriatic skin specimens. Supernatants prepared from these T cells were studied for their effects on keratinocyte proliferation in vitro. Conditioned media from 14 of 77 epidermal TCC, 7 of which were CD8⁺, and from 8 of 28 dermal TCC, 5 of which were CD8⁺, reproducibly enhanced keratinocyte proliferation, with more pronounced mitogenic activities found in dermal TCC. Another 9 epidermal and 3 dermal TCC did not affect keratinocyte growth and supernatants from the remaining clones, as well as from the 5 epidermal and 5 dermal TCL, inhibited keratinocyte replication to varying degrees. Both mitogenic and suppressive activities were largely abolished by addition of an antiserum to interferon-gamma (IFN-γ), while addition of epidermal growth factor or irradiated psoriatic TCL had little effect on the activities of the supernatants. These studies reveal that a subpopulation of lesional psoriatic T lymphocytes is capable of enhancing keratinocyte proliferation in vitro via secreted products. Their mitogenic capacity most likely requires IFN-γ, but the ultimate effect is apparently determined by the presence of additional cytokines. Activation of T cells secreting such combinations of factors in vivo may contribute to the keratinocyte alterations characteristic of psoriatic skin lesions.     

小鼠闭合性创伤对脾淋巴细胞增殖活性的影响

本文采用闭合性创伤模型,观察了单纯创伤因素对小鼠脾淋巴细胞增殖活性的影响。结果显示,伤后脾淋巴细胞自发母细胞转化(SBT)活性增强,而分裂原刺激的母细胞转化(MSBT)活性相应降低。提示无外源性感染的单纯创伤对淋巴细胞功能存明显的影响。     

雷公藤多甙对胶原诱导性关节炎大鼠IL-10表达的影响

目的研究雷公藤多甙对类风湿关节炎大鼠的作用,探讨类风湿关节炎的发病机制及雷公藤多甙的作用机制,为临床应用提供理论基础。方法本实验应用鸡Ⅱ型胶原蛋白,建立胶原诱导性关节炎(collagen-induced arthritis,CIA)大鼠模型。应用酶联免疫吸附试验方法(ELISA)检测观察正常对照组、CIA模型组和雷公藤多甙治疗组大鼠血液及关节液中白细胞介素-10(interleukin-10,IL-10)的浓度。结果 ELISA检测结果显示,类风湿关节炎大鼠血清和关节液中IL-10含量明显减低,而雷公藤多甙可以升高IL-10的浓度,使之趋向正常。结论雷公藤多甙可有效减轻佐剂型关节炎大鼠的关节病变,并能使CIA大鼠血清、关节浸液IL-10分子水平增高。     

The human peripheral lymphocyte—a model system for studying the combined effect of psoralen plus black light

Summary The effect of psoralen plus long wavelength ultraviolet light (UVA) on³H-thymidine uptake of PHA stimulated human lymphocytes was investigated. PHA induced lymphocyte transformation was inhibited by the combined action of psoralen and UVA irradiation in a dose related manner. Inhibition of DNA-synthesis occurred at concentrations of psoralen that can be expected in the serum of patients treated by systemic photochemotherapy. No effect was noted at these psoralen concentrations in the absence of UVA irradiation. Also did UVA irradiation in the absence of psoralen not inhibit³H-thymidine incorporation into PHA stimulated lymphocytes.     

大鼠骨髓间充质干细胞对淋巴细胞增殖影响的体外实验

目的：探讨大鼠骨髓间充质干细胞对淋巴细胞增殖的影响。方法：常规分离培养大鼠的骨髓间充质干细胞（MSCs）及淋巴细胞,灭活后的骨髓间充质干细胞和淋巴细胞混合培养48h后,MTT法检测淋巴细胞的相对细胞数,Hoechst 33258染色观察细胞核变化。结果：MTT结果显示,加入MSCs组OD值明显低于未加MSCs的对照组（p〈0．05）。Hoechst 33258染色显示MSCs组淋巴细胞有核回缩及凋亡小体出现。结论：MSCs对淋巴细胞的增殖有抑制作用,其作用机制可能与细胞凋亡有关。     

Distribution of Malassezia species on the skin of patients with psoriasis

IntroductionMalassezia species can induce the expression of interleukin-17 (IL-17), which plays an important role in the inflammatory and immune response in psoriasis (PS). The purpose of this study was to investigate the Malassezia species composition in patients with PS and healthy individuals and explore the role of Malassezia species in the pathogenesis of PS.Materials and methodsA total of 28 patients with PS and 10 age- and sex-matched healthy individuals participated in this study. Specimens collected from the lesional and non-lesional skin of patients with PS and the skin of healthy individuals were analyzed by using nested PCR.ResultsThe relative abundance of Malassezia species was 84.96% in healthy subjects, more than twice that in patients with PS (P < 0.01). M. restricta (43.09%) and M. globosa (41.38%) were the main Malassezia species in patients with PS followed by M. furfur (4.84%) and M. sympodialis (2.49%). M. sympodialis accounted for 18. 81% of the Malassezia species in healthy subjects, which was nearly eight times higher than in patients with PS (P < 0.01). Further, M. furfur was detected both on lesional and non-lesional psoriatic skin, but it was not found on the skin of healthy individuals.ConclusionsThe Malassezia species composition in patients with PS differed from that of healthy individuals. M. restricta and M. globosa were the main Malassezia species in patients with PS.     

Plasma inhibition of lymphocyte proliferation in nephrotic syndrome: Correlation with hyperlipidemia

Plasma-mediated inhibition of normal lymphoproliferation is an unexplained immunologic abnormality frequently observed in nephrotic syndrome. Since hyperlipidemia, also common in nephrotic syndrome, has been linked within vitro andin vivo immunodeficiency in other diseases, we have quantitated plasma-mediated inhibition of lymphoproliferation and related it to the degree of hyperlipidemia in 19 patients with nephrotic syndrome. Fifteen patients were hyperlipidemic; the plasma of 9 of these 15 caused >60% inhibition of antigen-specific proliferative responses of normal lymphocytes. None of the four normolipidemic plasmas, nor a hyperlipidemic plasma depleted of lipoproteins by ultracentrifugation, was inhibitory. A highly significant correlation between the degree of inhibition and the plasma triglyceride levels in patients with nephrotic syndrome was observed (P<0.001). The results suggest that elevated plasma lipids may be the cause of the plasma-mediated inhibition of lymphoproliferation in nephrotic syndrome.     

茯苓多糖对免疫抑制小鼠粘膜淋巴组织及脾脏中CD3~+和CD19~+细胞变化的影响

目的:通过研究口服茯苓多糖对环磷酰胺诱导的小鼠淋巴细胞亚群变化的作用,探讨茯苓多糖对肠道粘膜免疫与外周免疫系统作用的差异。方法:连续两周灌胃给予小鼠200 mg/(kg.d)茯苓多糖,在第14天腹腔注射100 mg/kg的环磷酰胺诱导免疫抑制模型,24小时后处死小鼠分别取派氏结(PPs)、肠系膜淋巴结(MLNs)和脾脏(SP)细胞,进行CD3+、CD19+双色免疫荧光标记,上流式细胞仪检测。结果:腹腔注射100 mg/kg的环磷酰胺后,小鼠PPs、MLNs和SP中的CD3+细胞比例上升,CD19+细胞比例下降,口服茯苓多糖可以明显的对抗PPs、MLNs中的CD3+、CD19+细胞比例的变化,但对SP中的CD3+、CD19+细胞比例的变化的作用不显著。结论:口服茯苓多糖能有效对抗环磷酰胺诱导的淋巴细胞亚群的变化,尤其是对PPs作用明显,提示茯苓多糖对肠道粘膜免疫系统的作用强于对外周免疫系统的作用。     

Relationship between retinal sensitivity and disease activity in patients with psoriasis vulgaris

OBJECTIVES:

Psoriasis is a hyperproliferative chronic inflammatory skin disease of unknown etiology and ocular structures and visual pathways can also be affected during the course of this disease. Subclinical optic neuritis has previously been observed in psoriatic patients in visual evoked potential studies. This trial was designed to evaluate retinal sensitivity in patients with psoriasis vulgaris.

METHODS:

A total of 40 eyes of 40 patients with chronic plaque-type psoriasis and 40 eyes of 40 age- and sex-matched control subjects were included in this study. The diagnosis of psoriasis was confirmed by skin biopsy. The severity was determined using the Psoriasis Area and Severity Index and the duration of the disease was recorded. After a full ophthalmological examination, including tests for color vision and pupil reactions, the visual field of each subject was assessed using both standard achromatic perimetry and short wavelength automated perimetry.

RESULTS:

The mean Psoriasis Area and Severity Index was 22.05±6.40′. There were no significant differences in the visual field parameters of subjects versus controls using either method. There were correlations between disease severity and the mean deviations in standard achromatic perimetry and short wavelength automated perimetry and between disease severity and the corrected pattern standard deviation and pattern standard deviation of short wavelength automated perimetry (r = -0.363, r = -0.399, r = 0.515 and r = 0.369, respectively).

CONCLUSIONS:

Retinal sensitivity appears to be affected by the severity of psoriasis vulgaris.     

Functional analysis of mononuclear cells infiltrating into tumors. VI. The effect of lymphocyte chemotactic factors on lymphocyte adhesion to endothelial cells.

We have analyzed mechanisms controlling infiltration of T lymphocytes into tumor tissues. A lymphocyte chemotactic factor-b (LMF-b) produced by tumor infiltrating CD4+ T lymphocytes was purified. LMB-b was specifically chemotactic for CD8+ T lymphocyte. Furthermore, LMF-b augmented lymphocyte adhesion to high endothelial venule (HEV) cells. The binding of CD8+ T cells to HEV cells was specifically augmented by LMF-b. The LMF-b primarily acted on T lymphocytes, whereas tumor necrosis factor as well as IFN-gamma acted on HEV cells or fibroblast cells. The binding of lymphocytes to fibroblast cell line was not augmented by LMF-b. The augmentation of lymphocyte adhesion to endothelial cells by LMF-b was mediated by the lymphocyte function associated antigen-1/intercellular adhesion molecule (LFA-1/ICAM) pathway, the CD2/LFA-3 pathway, and the very late antigen-4/culture supernatant-1 (VLA-4/CS-1) pathway.