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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2013

Open Access 01-12-2013 | Research

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

Authors: Minchao Cai, Jing Wu, Chaoming Mao, Jianmin Ren, Pu Li, Xiao Li, Jiuchang Zhong, Chundi Xu, Tong Zhou

Published in: Journal of Translational Medicine | Issue 1/2013

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Abstract

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.
Appendix
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Metadata
Title
A Lectin-EGF antibody promotes regulatory T cells and attenuates nephrotoxic nephritis via DC-SIGN on dendritic cells
Authors
Minchao Cai
Jing Wu
Chaoming Mao
Jianmin Ren
Pu Li
Xiao Li
Jiuchang Zhong
Chundi Xu
Tong Zhou
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2013
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-11-103

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