A Lectin-EGF antibody promotes regulatory T cells and attenuates nephrotoxic nephritis via DC-SIGN on dendritic cells

被引：10

作者：

Cai, Minchao ^{[1
,2
]}

Wu, Jing ^{[1
]}

Mao, Chaoming ^{[3
,4
,5
]}

Ren, Jianmin ^{[1
]}

Li, Pu ^{[1
]}

Li, Xiao ^{[2
]}

Zhong, Jiuchang ^{[6
,7
]}

Xu, Chundi ^{[1
]}

Zhou, Tong ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Dept Pediat, Ruijin Hosp, Shanghai 200025, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Nephrol, Shanghai 200025, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Shanghai 200025, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Shanghai 200025, Peoples R China

[5] Jiangsu Univ, Affiliated Hosp, Dept Nucl Med, Zhenjiang 212001, Peoples R China

[6] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Shanghai 200025, Peoples R China

[7] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai Inst Hypertens, Shanghai 200025, Peoples R China

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2013年 / 11卷

基金：

中国国家自然科学基金;

关键词：

DC-SIGN; Dendritic cells; Regulatory T cells; Glomerulonephritis; C-TYPE LECTINS; EXPERIMENTAL GLOMERULONEPHRITIS; CRESCENTIC GLOMERULONEPHRITIS; RENAL-FAILURE; INDUCE; TOLERANCE; RESPONSES; IMMUNITY; MICE; TH1;

D O I：

10.1186/1479-5876-11-103

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Background: Interactions between dendritic cells (DCs) and T cells play a critical role in the development of glomerulonephritis, which is a common cause of chronic kidney disease. DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), an immune-regulating molecule of the C-type lectin family, is mainly expressed on DCs and mediates DC adhesion and migration, inflammation, activation of primary T cells. DC-SIGN triggers immune responses and is involved in the immune escape of pathogens and tumours. In addition, ligation of DC-SIGN on DCs actively primes DCs to induce Tregs. Under certain conditions, DC-SIGN signalling may result in inhibition of DC maturation, by promoting regulatory T cell (Treg) function and affecting Th1/Th2 bias. Methods: A rat model of nephrotoxic nephritis was used to investigate the therapeutic effects of an anti-lectin-epidermal growth factor (EGF) antibody on glomerulonephritis. DCs were induced by human peripheral blood mononuclear cells in vitro. The expression of DC surface antigens were detected using flow cytometry; the levels of cytokines were detected by ELISA and qPCR, respectively; the capability of DCs to stimulate T cell proliferation was examined by mixed lymphocyte reaction; PsL-EGFmAb targeting to DC-SIGN on DCs was identified by immunoprecipitation. Results: Anti-Lectin-EGF antibody significantly reduced global crescent formation, tubulointerstitial injury and improved renal function impairment through inhibiting DC maturation and modulating Foxp3 expression and the Th1/Th2 cytokine balance in kidney. Binding of anti-Lectin-EGF antibody to DC-SIGN on human DCs inhibited DC maturation, increased IL-10 production from DCs and enhanced CD4(+)CD25(+) Treg functions. Conclusions: Our results suggest that treatment with anti-Lectin-EGF antibody modulates DCs to suppressive DCs and enhances Treg functions, contributing to the attenuation of renal injury in a rat model of nephrotoxic nephritis.

引用

页数：14

共 43 条

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