title: A Lectin-EGF antibody promotes regulatory T cells and attenuates nephrotoxic nephritis via DC-SIGN on dendritic cells.
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.
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Minchao
authors.initials: M
authors.lastname: Cai
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Chaoming
authors.initials: C
authors.lastname: Mao
authors.forename: Jianmin
authors.initials: J
authors.lastname: Ren
authors.forename: Pu
authors.initials: P
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Jiuchang
authors.initials: J
authors.lastname: Zhong
authors.forename: Chundi
authors.initials: C
authors.lastname: Xu
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000954:Antigens, Surface / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000737:chemistry*; D006801:Humans; D007249:Inflammation; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000293:injuries; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D009393:Nephritis / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D011921:Rats, Inbred WKY; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D004815:Epidermal Growth Factor; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin