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. 2014 Dec 15;7(12):4846-56.
eCollection 2014.

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

Zhengdong Fang  1 , Qiong Deng  1 , Hejie Hu  1 , Xiaotian Wang  1 , Xiaojie Sun  1 , Xinbao Ge  1 , Peishuang Wang  1
Affiliations

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

Zhengdong Fang et al. Int J Clin Exp Med. .

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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Figures

Figure 1
Figure 1
Attenuated TDC in vessel wall of ASO and diabetic foot patients compared to healthy person (200 ×). A. Representative images of CD11b-expressing TDC (left) and DC-SIGN-expressing TDC (right) in the vessel wall of healthy person. B. Representative images of CD11b-expressing TDC (left) and DC-SIGN-expressing TDC (right) in the vessel wall of ASO patients. C. Representative images of CD11b-expressing TDC (left) and DC-SIGN-expressing TDC (right) in the vessel wall of diabetic foot patients.
Figure 3
Figure 3
Quantification analyzed the expression of TDC and mDC in ASO and diabetic foot patients. A. Western blotting analyzed the expression of CD1a and CD83 in TDC and CD11b and DC-SIGN in mDC of ASO and diabetic foot patients. B. Quantification of the protein DC-SIGN and CD11b expression by image analysis. C. Quantification of the protein CD83 and CD1a expression by image analysis. Data are presented as the mean ± SD values of triplicate cultures. Representative data from three independent experiments were presented. *P < 0.05; **P < 0.01 versus normal people; ##P < 0.01 versus ASO patients.
Figure 2
Figure 2
Increased mDC in vessel wall of ASO and diabetic foot patients compared to healthy person (200 ×). A. Representative images of the expression of CD1a in mDC (left) and the expression of CD83 in mDC (right) in healthy human vascular wall. B. Representative images of the expression of CD1a in mDC (left) and the expression of CD83 in mDC (right) in ASO patients vascular wall. C. Representative images of the expression of CD1a in mDC (left) and the expression of CD83 in mDC (right) in diabetic foot patients vascular wall.
Figure 4
Figure 4
CD11c+CD11b+TDC and CD11c+CD83+mDC were induced successfully and displayed tolerogenic phenotype. A. Left dots plot showed that the ratio of rmGM-CSF and IL-4 induced CD11c+CD11b+TDC was approximately 41.5%, and right dots plot showed that the ratio of LPS-induced CD11c+CD83+mDC was approximately 60.1%. B. Compared with LPS induced mDCs, CD11b+F4/80+ TDCs secreted significantly high levels of IL-10 and TGFβ1. #P < 0.05; ##P < 0.01 versus mDC.
Figure 5
Figure 5
TDC inhibited the functions of Th17 cells while mDC promoted the differentiation of Th17 cells in vitro. A. TDCs inhibited the generation of Th17 cells in vitro. The percentage of CD4+IL-17+ Th17 cells were significantly decreased when co-cultured with TDC. And the percentage of CD4+IL-17+ Th17 cells were significantly increased when co-cultured with mDC. B. Histogram showed that TDC inhibited the differentiation of Th17 cells while mDC promoted the differentiation of Th17 cells in vitro. C. TDCs inhibited the expressions of IL-17 mRNA in Th17 cells in vitro. Compared with controls group, the expression of IL-17 mRNA in T lymphocytes was decreased when co-cultured with TDC, and the expression of IL-17 mRNA in T lymphocytes was increased when co-cultured with mDC. D. Quantification of the gene expression by image analysis. E. TDCs inhibited the level of IL-17 in Th17 cells in vitro. Histogram showed that the level of IL-17 in cells supernatants was decreased when co-cultured with TDC, and the expression of IL-17 in cells supernatants was increased when co-cultured with mDC. Data are presented as the mean ± SD values of triplicate cultures. Representative data from three independent experiments were presented. **P < 0.01 versus T cell; #P < 0.05; ##P < 0.01 versus T cells + PMA + Ion + BFA.
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