DC-SIGN modulates DC maturation and function in rat renal tubulointerstitial lesions.
The role of DC-SIGN in tubulointerstitial lesions (TILs) and the effect of anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) were investigated in rat nephrotoxic nephritis (NTN). On Day 4, immature DC-SIGN+DCs infiltrated into renal tubulointerstitium and matured by Day 14, showing increased migratory capacity and ability to induce T cell proliferation. The distribution of DC-SIGN+ DC significantly correlated with crescent formation, TIL severity, and changes in renal function. RANTES and TNF-alpha mRNA were continuously up-regulated from Day 4, while IL-10 mRNA was down-regulated after a marked increase on Day 4. Expression of IFN-gamma and IL-4 mRNA increased on Day 14 due to DC maturation. PsL-EGFmAb suppressed DC maturation, migration and ability to activate T cells. It also down-regulated TNF-alpha and up-regulated IL-10, resulting in a Th1/Th2 bias. The number of crescents decreased and TILs and renal function improved. These results suggest that DC-SIGN mediates DC tubulointerstitial infiltration and is an important regulator of local immune reactions and TILs. PsL-EGFmAb inhibited DC migration, maturation and function by targeting DC-SIGN, and may therefore be a potential treatment for NTN.
Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
Minchao
M
Cai
Tong
T
Zhou
Xiao
X
Li
Jing
J
Chen
Chaoming
C
Mao
Xiaodong
X
Xi
Nan
N
Chen
Chundi
C
Xu
D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000502:physiology*; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers; D003713:Dendritic Cells / Q000166:cytology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D037181:Lectins, C-Type / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D016207:Cytokines; D017931:DNA Primers; D037181:Lectins, C-Type; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin