树突细胞DC-LAMP和DC-SIGN在寻常型银屑病皮损中的表达及意义

发布时间：2018-07-06 19:58

本文选题：银屑病 + T淋巴细胞　；参考：《山东大学》2010年硕士论文

【摘要】： 研究背景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分化、真皮浅层炎细胞浸润和血管增生扩张为基本病理特点。目前主要在免疫紊乱、表皮角质形成细胞异常增殖和微血管增生异常等方面研究其发病机制,较一致的观点认为银屑病是一种多基因遗传背景下的免疫介导的炎症性皮肤病,免疫紊乱与银屑病发生、发展及反复发作密切相关。皮损中的T淋巴细胞异常活化是银屑病病发生的关键,同时有树突细胞、角质形成细胞等多种免疫细胞及细胞因子的参与,共同构成银屑病的免疫发病过程。树突细胞具有激活静止T淋巴细胞必需的所有特性,未成熟树突细胞具有较强的摄取和加工抗原的功能,成熟的树突细胞具有较强的递呈抗原功能。树突细胞与T淋巴细胞在银屑病免疫机制中的关系日益受到研究者们的重视。树突细胞的成熟标志DC-LAMP (DC-lysosomal-associated membrane protein,即CD208),是溶酶体相关膜蛋白(LAMP)家族的成员之一,其功能与树突细胞内MHC抗原复合物的加工和胞内运输过程有关。DC-SIGN (dendritic-cell specific ICAM-3 grabbing non-integrin,即CD209),是新发现的一种特异性表达在树突细胞上的C-型凝集素,调节树突细胞的多种免疫功能,在激活T淋巴细胞方面具有重要作用。DC-LAMP和DC-SIGN是调节树突细胞与T淋巴细胞相互作用的两个关键因子。研究目的检测DC-LAMP与DC-SIGN在寻常型银屑病皮损组织中的表达,观察其在寻常型银屑病皮损组织与正常组织中表达水平的差异及相关性,探讨DC-LAMP与DC-SIGN在银屑病发病机制中的作用。研究方法利用RT-PCR法和免疫组化法检测33例寻常型银屑病皮损组织和11例正常皮肤组织石蜡包埋组织标本中DC-LAMP、DC-SIGN的表达与定位。采用图像分析技术定量分析寻常型银屑病组织皮损与正常组织中DC-LAMP与DC-SIGN的表达差异,并进行相关性分析。结果PCR结果显示银屑病组和正常组皮肤均扩增出符合要求的目的片段,银屑病组DC-LAMP、DC-SIGN的基因表达水平均高于正常皮肤组。寻常型银屑病皮损处DC-LAMP的阳性表达位于角质形成细胞的基底层、棘层和真皮树突细胞的胞浆中；DC-SIGN的阳性表达位于基底层、棘细胞层角质形成细胞和真皮树突细胞的胞浆、胞核中。DC-LAMP及DC-SIGN在寻常型银屑病皮损组织中的表达明显高于正常对照组,其差异具有统计学意义(P0.01)；DC-LAMP与DC-SIGN在寻常型银屑病皮损组织中的表达呈正相关(P0.05,r=0.368)。结论①DC-LAMP表达在寻常型银屑病皮损内表皮角质形成细胞、真皮浅层树突细胞的胞浆中,其基因转录水平和蛋白表达水平均明显高于正常皮肤。②DC-SIGN表达在寻常型银屑病皮损内表皮角质形成细胞、真皮浅层树突细胞的胞浆和胞核中,其基因转录水平和蛋白表达水平均明显高于正常皮肤。③DC-LAMP与DC-SIGN在银屑病皮损的高表达呈正相关,提示DC-LAMP和DC-SIGNP可能具有协同刺激T淋巴细胞活化的作用。④银屑病角质形成细胞表达DC-LAMP、DC-SIGN,参与皮损内T淋巴细胞继续活化。
[Abstract]:Background psoriasis is a common chronic inflammatory dermatosis. It is characterized by abnormal proliferation and differentiation of keratinocytes, infiltration of superficial dermatitis cells and proliferation of vascular proliferation. The pathogenesis is mainly in the aspects of immune disorder, abnormal proliferation of epidermal keratinocytes and abnormal blood Guan Zengsheng. The point of view is that psoriasis is an immune mediated inflammatory dermatosis in the genetic background of multiple genes. The immune disorder is closely related to the occurrence of psoriasis, development and recurrent attacks. The abnormal activation of T lymphocytes in the skin is the key to the occurrence of psoriasis, and there are many immune cells and fine cells, such as dendritic cells, keratinocytes, and so on. The participation of cytokines contributes to the pathogenesis of psoriasis.
Dendritic cells have all the necessary characteristics to activate static T lymphocytes. Immature dendritic cells have strong ability to absorb and process antigens. Mature dendritic cells have strong antigen presenting function. The relationship between dendritic cells and T lymphocytes in the immune mechanism of psoriasis is being paid more and more attention by researchers. The maturation marker, DC-LAMP (DC-lysosomal-associated membrane protein, CD208), is one of the members of the lysosomal related membrane protein (LAMP) family. Its function is related to the processing of the MHC antigen complex in the dendritic cells and the intracellular transport process associated with.DC-SIGN (dendritic-cell specific ICAM-3 grabbing), which is a new discovery. A type of C- agglutinin specifically expressed on dendritic cells, regulating various immune functions of dendritic cells and playing an important role in activating T lymphocytes,.DC-LAMP and DC-SIGN are two key factors regulating the interaction of dendritic cells and T lymphocytes.
Objective to detect the expression of DC-LAMP and DC-SIGN in the skin lesions of psoriasis vulgaris, to observe the difference and correlation between the expression level of psoriasis vulgaris and normal tissues, and to explore the role of DC-LAMP and DC-SIGN in the pathogenesis of psoriasis.
The expression and localization of DC-LAMP and DC-SIGN in 33 cases of psoriasis vulgaris skin tissue and 11 normal skin tissue specimens were detected by RT-PCR and immunohistochemistry. The difference between the tissue skin lesions of psoriasis vulgaris and the expression of DC-LAMP and DC-SIGN in normal fabric was analyzed by image analysis. Correlation analysis.
Results the results of PCR showed that both the psoriasis group and the normal group amplified the desired target segments. The expression level of DC-LAMP and DC-SIGN in psoriasis group was higher than that in the normal skin group. The positive expression of DC-LAMP in psoriasis vulgaris lesions was located in the basal layer of keratinocytes, the spinous and dermis dendritic cells in the cytoplasm; DC-SIGN The positive expression was located in the basal layer, the acanthocyte layer keratinocyte and the cytoplasm of the dermis dendritic cells. The expression of.DC-LAMP and DC-SIGN in the skin lesions of psoriasis vulgaris was significantly higher than that of the normal control group, and the difference was statistically significant (P0.01). The expression of DC-LAMP and DC-SIGN in the skin lesions of psoriasis vulgaris Positive correlation (P0.05, r=0.368).
Conclusion (1) the expression of DC-LAMP in the epidermis of epidermal keratinocytes in psoriasis vulgaris and in the cytoplasm of the superficial dendritic cells of the dermis is significantly higher than that of the normal skin. (2) the expression of DC-SIGN in the epidermis of the epidermis and the nucleus of the superficial dendrite cells in the skin of psoriasis vulgaris. The gene transcription level and protein expression level were significantly higher than normal skin. (3) DC-LAMP and DC-SIGN were positively correlated with the high expression of psoriatic skin lesions, suggesting that DC-LAMP and DC-SIGNP may have synergistic stimulation of T lymphocyte activation. 4. Keratinocytes of psoriasis express DC-LAMP, DC-SIGN, and participate in T lymphocytes in skin lesions. Continued activation.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R758.63

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