Infiltrating dendritic cells contribute to local synthesis of C1q in murine and human lupus nephritis.
Lupus nephritis causes morbidity and mortality in patients affected by Systemic Lupus Erythematosus (SLE). Recent data have shown that dendritic cells (DC) play a central role in SLE pathogenesis, by enhancing the presentation of auto-antigens and the induction of autoimmunity. In this paper we demonstrated in a mouse model of progressive lupus nephritis that C1q, the recognition unit of complement classical pathway, is locally produced in the kidney. This local renal synthesis of C1q increased in a time dependent manner in accordance with the recruitment of infiltrating MHC II+ antigen presenting cells. In vitro C1q was produced by immature bone-marrow derived DC and was down regulated upon LPS-induced maturation. Consistent with these data, confocal microscopy analysis showed that interstitial C1q was associated with myeloid CD11c+-DC. Finally, we showed that also in the kidney of SLE patients with severe lupus nephritis, but not in patients with mild nephritis, C1q was associated with BDCA1+ myeloid DC. These data suggest that renal DC are responsible for the local synthesis of C1q in lupus nephritis, a process that may contribute to local complement activation and facilitate the engulfment of apoptotic renal cells and the presentation of auto-antigens to the adaptive immune response.
Castellano
Giuseppe
G
Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Italy. g.castellano@nephro.uniba.it
Trouw
Leendert A
LA
Fiore
Nicoletta
N
Daha
Mohamed R
MR
Schena
F Paolo
FP
van Kooten
Cees
C
D000818:Animals; D015922:Complement C1q / Q000096:biosynthesis* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000276:immunology; D008181:Lupus Nephritis / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D015922:Complement C1q