title: Infiltrating dendritic cells contribute to local synthesis of C1q in murine and human lupus nephritis.
abstract: 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.
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Italy. g.castellano@nephro.uniba.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castellano
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Fiore
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: F Paolo
authors.initials: FP
authors.lastname: Schena
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D015922:Complement C1q