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
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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(P<0.01)；DC-LAMP与DC-SIGN在寻常型银屑病皮损组织中的表达呈正相关(P<0.05,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。
Research Background Psoriasis is a common chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation, superficial dermal inflammatory cell infiltration and vascular proliferation as the basic pathology. At the present,the study of it's pathogenesis is mainly in immune disorders, abnormal epidermal keratinocyte proliferation and abnormal capillary proliferation, etc. More consistent view is that psoriasis is a multi-genetic background of immune-mediated inflammatory skin disease, and the existence of immune disorders is closely related to the psoriasis occur, development and recurrence. The abnormal activation of T lymphocytes in psoriasis lesions is the key to the disease. Meanwhile, dendritic cells, keratinocytes and other immune cells with their cytokines constitute the immune pathogenesis of psoriasis together.
Dendritic cells possess all the features to activate naive T lymphocytes. Immature dendritic cells have strong antigen capture and processing functions, while Mature dendritic cells have strong antigen presenting functions.The relationship between Dendritic cells and T lymphocytes in the immune pathogenesis of psoriasis was attentioned by researchers. DC-lysosomal-associated membrane protein (DC-LAMP) is the marker of mature dendritic cells, belonging to lysosome associated membrane protein family. Its function is connected with processing MHC antigen complex and their intracellular transport in dendritic cells. Dendritic cell specific ICAM-3 grabbing non-integrin(DC-SIGN) is a newly discovered C-type lectin, expressed specificly in dendritic cells, regulating variety immune function of dendritic cells, playing an important role in Activated T lymphocytes. DC-LAMP and DC-SIGN are the key factors in regulation the relationship between dendritic cells and T lymphocytes.
Research Objective In the study, We investigated the expression of DC-LAMP and DC-SIGN in normal skin and psoriasis vulgaris lesions, to explore the role of DC-LAMP and DC-SIGN in the pathogenic mechanism associated with psoriasis.
Research Methods The expression and allocation of DC-LAMP and DC-SIGN were determined by immunohistochemistry and RT-PCR in 33 case psoriasis vulgaris paraffin imbedding samples, as well as in 11 case healthy individuals. Using image analysis technique, we analyzed the quantity of DC-LAMP and DC-SIGN expressed in psoriasis vulgaris and the normal skin. And their correlation analysis was performed.
Results The PCR results showed that both psoriasis group and the normal group all amplify the goal fragment. The gene level expressed by psoriasis lesions were higher than the normal skins. DC-LAMP highly expressed in the cytoplasm of basal layer, spinous layer epidermis and dendritic cells in dermis. DC-SIGN highly expressed in the cytoplasm and the cytoblast of keratinocytes and dendritic cells in dermis. The expression of DC-LAMP and DC-SIGN in psoriasis vulgaris tissue were significant higher than that of normal skin, showing statistical significance (P<0.01). And in psoriasis lesions, the expression of DC-LAMP was positively correlated with the expression of DC-SIGN (P<0.05, r=0.368)
Conclusions①DC-LAMP located in the cytoplasm of epidermis keratinocyte and dendritic cells in dermis of psoriasis vulgaris lesions. Its expression of gene level and protein level were significant higher than that of normal skin.②DC-SIGN located in the cytoplasm and the cytoblast of keratinocytes and dendritic cells in dermis. Its expression of gene level and protein level were significant higher than that of normal skin.③The result of DC-LAMP was positively correlated with DC-SIGN in psoriasis shows DC-LAMP in coordination with DC-SIGN participating T lymphocytes.④keratinocyte express DC-LAMP and DC-SIGN to active T lyphocytes deeply in psoriasis lesions.
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(P<0.01)；DC-LAMP与DC-SIGN在寻常型银屑病皮损组织中的表达呈正相关(P<0.05,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。
Research Background Psoriasis is a common chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation and differentiation, superficial dermal inflammatory cell infiltration and vascular proliferation as the basic pathology. At the present,the study of it's pathogenesis is mainly in immune disorders, abnormal epidermal keratinocyte proliferation and abnormal capillary proliferation, etc. More consistent view is that psoriasis is a multi-genetic background of immune-mediated inflammatory skin disease, and the existence of immune disorders is closely related to the psoriasis occur, development and recurrence. The abnormal activation of T lymphocytes in psoriasis lesions is the key to the disease. Meanwhile, dendritic cells, keratinocytes and other immune cells with their cytokines constitute the immune pathogenesis of psoriasis together.
Dendritic cells possess all the features to activate naive T lymphocytes. Immature dendritic cells have strong antigen capture and processing functions, while Mature dendritic cells have strong antigen presenting functions.The relationship between Dendritic cells and T lymphocytes in the immune pathogenesis of psoriasis was attentioned by researchers. DC-lysosomal-associated membrane protein (DC-LAMP) is the marker of mature dendritic cells, belonging to lysosome associated membrane protein family. Its function is connected with processing MHC antigen complex and their intracellular transport in dendritic cells. Dendritic cell specific ICAM-3 grabbing non-integrin(DC-SIGN) is a newly discovered C-type lectin, expressed specificly in dendritic cells, regulating variety immune function of dendritic cells, playing an important role in Activated T lymphocytes. DC-LAMP and DC-SIGN are the key factors in regulation the relationship between dendritic cells and T lymphocytes.
Research Objective In the study, We investigated the expression of DC-LAMP and DC-SIGN in normal skin and psoriasis vulgaris lesions, to explore the role of DC-LAMP and DC-SIGN in the pathogenic mechanism associated with psoriasis.
Research Methods The expression and allocation of DC-LAMP and DC-SIGN were determined by immunohistochemistry and RT-PCR in 33 case psoriasis vulgaris paraffin imbedding samples, as well as in 11 case healthy individuals. Using image analysis technique, we analyzed the quantity of DC-LAMP and DC-SIGN expressed in psoriasis vulgaris and the normal skin. And their correlation analysis was performed.
Results The PCR results showed that both psoriasis group and the normal group all amplify the goal fragment. The gene level expressed by psoriasis lesions were higher than the normal skins. DC-LAMP highly expressed in the cytoplasm of basal layer, spinous layer epidermis and dendritic cells in dermis. DC-SIGN highly expressed in the cytoplasm and the cytoblast of keratinocytes and dendritic cells in dermis. The expression of DC-LAMP and DC-SIGN in psoriasis vulgaris tissue were significant higher than that of normal skin, showing statistical significance (P<0.01). And in psoriasis lesions, the expression of DC-LAMP was positively correlated with the expression of DC-SIGN (P<0.05, r=0.368)
Conclusions①DC-LAMP located in the cytoplasm of epidermis keratinocyte and dendritic cells in dermis of psoriasis vulgaris lesions. Its expression of gene level and protein level were significant higher than that of normal skin.②DC-SIGN located in the cytoplasm and the cytoblast of keratinocytes and dendritic cells in dermis. Its expression of gene level and protein level were significant higher than that of normal skin.③The result of DC-LAMP was positively correlated with DC-SIGN in psoriasis shows DC-LAMP in coordination with DC-SIGN participating T lymphocytes.④keratinocyte express DC-LAMP and DC-SIGN to active T lyphocytes deeply in psoriasis lesions.
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