C5a/C5aR Pathway initiates the Psoriasis skin Inflammation by potentiating Plasmacytoid Dendritic Cell Function
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- 英文论文题名：C5a/C5aR Pathway initiates the Psoriasis skin Inflammation by potentiating Plasmacytoid Dendritic Cell Function
- 论文作者：Zheng Quanyou ; Liang Shenju ; Yan Leyu ; Li Guiqin ; Xu Guilian ; Zhang Keqin
- 英文论文作者：Zheng Quanyou ; Liang Shenju ; Yan Leyu ; Li Guiqin ; Xu Guilian ; Zhang Keqin ; Department of Nephrology ; Southwest Hospital ; Third Military Medical University ; Department of Rheumatism and Immunology ; Daping Hospital ; Third Military Medical University ; Department of Immunology ; Third Military Medical University
- 年：2016
- 作者机构：Department of Nephrology,Southwest Hospital,Third Military Medical University;Department of Rheumatism and Immunology,Daping Hospital,Third Military Medical University;Department of Immunology,Third Military Medical University;
- 英文论文关键词：Psoriasis ; C5a/C5aR pathway ; pDCs
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R758.63
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：1328k
- 原文格式：D
- 会议级别：全国
摘要
Objective: Psoriasis is one of the most common chronic inflammatory skin diseases, affects ~2% of the population all over the world. Lacking understanding of psoriasis pathogenesis has in essence hindered efficient clinic treatment. Increasing evidence indicate that the complement system performs an essential role in the development of psoriasis. Herein, we investigated the effect of C5a/C5 a R pathway in the pathogenesis of psoriasis and explored the underlying mechanism. Methods: The psoriasis like skin inflammation was monitored and histological changes of skin were also assessed following 6 consecutive days of IMQ application. Gene expression coding inflammatory cytokines and chemotactic factors were tested. The expansion of plasmacytoid dendritic cells(p DCs) was analyzed by Flow cytometry and immune histological staining both in vivo and in vitro. At last, functions of p DCs were also examined by stimulating with IMQ in vitro.Results: At the macroscopic level, scaly skin inflammation induced by daily applications of IMQ in wild-type mice were significantly attenuated in C5 a R deficient mice or in mice treated with an antagonist of C5 a R(C5a Ra). At the microscopic level, C5 a R deficient mice showed a dramatic decrease in keratinocytes proliferation, vascular remodel and T cells infiltration. At the molecular level, the absence or inhibition of C5 a R strongly decreased the expression of cytokines, chemotactic factors and keratin 10, which reflects hyper-proliferation responses of keratinocytes. C5 a R also played a critical role in neutrophil and p DCs infiltration after IMQ application. In addition, the production of IFN-α by C5 a R-deficient p DC was remarkably reduced after being stimulated with IMQ in vitro. Conclusion: These results provide evidence that C5 a R is required for the pathogenesis of psoriasis skin lesion in the mouse IMQ model and C5 a R is crucial for p DCs expansion and type I IFN production. Inhibition of C5a/C5 a R pathway is expected to be beneficial in the clinical treatment of psoriasis patients.
Objective: Psoriasis is one of the most common chronic inflammatory skin diseases, affects ~2% of the population all over the world. Lacking understanding of psoriasis pathogenesis has in essence hindered efficient clinic treatment. Increasing evidence indicate that the complement system performs an essential role in the development of psoriasis. Herein, we investigated the effect of C5a/C5 a R pathway in the pathogenesis of psoriasis and explored the underlying mechanism. Methods: The psoriasis like skin inflammation was monitored and histological changes of skin were also assessed following 6 consecutive days of IMQ application. Gene expression coding inflammatory cytokines and chemotactic factors were tested. The expansion of plasmacytoid dendritic cells(p DCs) was analyzed by Flow cytometry and immune histological staining both in vivo and in vitro. At last, functions of p DCs were also examined by stimulating with IMQ in vitro.Results: At the macroscopic level, scaly skin inflammation induced by daily applications of IMQ in wild-type mice were significantly attenuated in C5 a R deficient mice or in mice treated with an antagonist of C5 a R(C5a Ra). At the microscopic level, C5 a R deficient mice showed a dramatic decrease in keratinocytes proliferation, vascular remodel and T cells infiltration. At the molecular level, the absence or inhibition of C5 a R strongly decreased the expression of cytokines, chemotactic factors and keratin 10, which reflects hyper-proliferation responses of keratinocytes. C5 a R also played a critical role in neutrophil and p DCs infiltration after IMQ application. In addition, the production of IFN-α by C5 a R-deficient p DC was remarkably reduced after being stimulated with IMQ in vitro. Conclusion: These results provide evidence that C5 a R is required for the pathogenesis of psoriasis skin lesion in the mouse IMQ model and C5 a R is crucial for p DCs expansion and type I IFN production. Inhibition of C5a/C5 a R pathway is expected to be beneficial in the clinical treatment of psoriasis patients.
Objective: Psoriasis is one of the most common chronic inflammatory skin diseases, affects ~2% of the population all over the world. Lacking understanding of psoriasis pathogenesis has in essence hindered efficient clinic treatment. Increasing evidence indicate that the complement system performs an essential role in the development of psoriasis. Herein, we investigated the effect of C5a/C5 a R pathway in the pathogenesis of psoriasis and explored the underlying mechanism. Methods: The psoriasis like skin inflammation was monitored and histological changes of skin were also assessed following 6 consecutive days of IMQ application. Gene expression coding inflammatory cytokines and chemotactic factors were tested. The expansion of plasmacytoid dendritic cells(p DCs) was analyzed by Flow cytometry and immune histological staining both in vivo and in vitro. At last, functions of p DCs were also examined by stimulating with IMQ in vitro.Results: At the macroscopic level, scaly skin inflammation induced by daily applications of IMQ in wild-type mice were significantly attenuated in C5 a R deficient mice or in mice treated with an antagonist of C5 a R(C5a Ra). At the microscopic level, C5 a R deficient mice showed a dramatic decrease in keratinocytes proliferation, vascular remodel and T cells infiltration. At the molecular level, the absence or inhibition of C5 a R strongly decreased the expression of cytokines, chemotactic factors and keratin 10, which reflects hyper-proliferation responses of keratinocytes. C5 a R also played a critical role in neutrophil and p DCs infiltration after IMQ application. In addition, the production of IFN-α by C5 a R-deficient p DC was remarkably reduced after being stimulated with IMQ in vitro. Conclusion: These results provide evidence that C5 a R is required for the pathogenesis of psoriasis skin lesion in the mouse IMQ model and C5 a R is crucial for p DCs expansion and type I IFN production. Inhibition of C5a/C5 a R pathway is expected to be beneficial in the clinical treatment of psoriasis patients.
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