Abstract
BackgroundInteractions 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.MethodsA 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.ResultsAnti-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.ConclusionsOur 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.
Highlights
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
We demonstrated that DCs treated in vitro with an anti-lectin-epidermal growth factor (EGF) domain monoclonal antibody originally developed against P-selectin (PsL-EGFmAb) displayed low expression of co-stimulatory molecules and an impaired capability to stimulate CD4+ T cells [26], indicating suppression of DC maturation and function
In the PsL-EGFmAb-treated group, we observed a significant reduction in levels of urinary 24-hour proteins, blood urea nitrogen (BUN) and Serum creatintine (Scr), and increased Creatinine clearance (Ccr) levels compared with the nephrotoxic nephritis (NTN) group (p < 0.01), indicating that PsL-EGFmAb treatment improved renal function
Summary
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. Mature DCs induce Th1, Th2 and Th17 effector T-cells, whereas immature DCs drive the development of regulatory T cells (Tregs), which maintain tolerance to self-antigens and inhibit excessive immune responses by producing IL-10 and TGF-β [9,10,11,12,13,14]. DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), a member of the C-type lectin family, mediates DC adhesion and migration, inflammation, activation of primary T cells, contributes to immune responses and the immune escape of pathogens and tumors [21,22,23]. Targeting DC-SIGN may be a useful strategy to suppress inflammatory responses, which could be beneficial in managing autoimmunity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
