Characteristics of immunogenic and tolerogenic dendritic cells within the arterial wall in atherosclerosis and in vitro

动脉粥样硬化及体外动脉壁内免疫原性和耐受性树突状细胞的特征

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作者:Zhengdong Fang ,Qiong Deng ,Hejie Hu ,Xiaotian Wang ,Xiaojie Sun ,Xinbao Ge ,Peishuang Wang

Abstract

Aim: To investigate the characteristic of mature dendritic cell (mDC) and tolerogenic dendritic cell (TDC) in human lower limb atherosclerosis occlusion syndrome (ASO) and diabetic foot and in vitro. Methods: 58 human ASO and diabetic foot arterial specimens were collected from surgical operation and autopsy. Immunohistochemical and Western blotting method were used to examine the distribution and the content of CD83 and CD1a positive reaction mDC and CD11b and DC-SIGN positive reaction TDC. Furthermore, bone marrow-derived DCs were induced by rmGM-CSF and rmIL-4 in the presence or absence of LPS in vitro. The percent of CD11c(+)CD11b(+)TDC and CD11c(+)CD83(+)mDC were analyzed by flow cytometry. The effects of TDC and mDC on T lymphocytes were analyzed by the IL-17 level, the percent of Th17, and IL-17 mRNA expression. Results: Immunogenicity mDC was heavily found in intima plaque and around the small vessel of adventitia on artherosclerosis aorta of lesion group, and was positively correlated to the progress of the disease. However, there were low expression of TDC and was negatively correlated to the progress of the disease. Meanwhile, we found that there is a close relationship between high glucose and disease progression. TDC expressed high levels of IL-10 and TGF-β1 and down-regulated the percent of CD4(+)IL-17(+) Th17, IL-17 mRNA and the level of IL-17 in vitro. Conclusion: TDC and mDC are assembled in the process of ASO, and the progression of the disease might be aggravated by DC-maturation. High glucose might closely relate to the progression of atherosclerosis. Keywords: Dendritic cells; diabetic foot; immune response; immunogenicity; lower limb atherosclerosis occlusion syndrome; tolerogenicity.

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