Infiltrating dendritic cells contribute to local synthesis of C1q in murine and human lupus nephritis

• Published in: Molecular immunology Vol. 47; no. 11; pp. 2129 - 2137
• Main Authors: Castellano, Giuseppe, Trouw, Leendert A., Fiore, Nicoletta, Daha, Mohamed R., Schena, F. Paolo, van Kooten, Cees
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2010
• Subjects: Animals; C1q; Complement; Complement C1q - biosynthesis; Complement C1q - genetics; Dendritic cell; Dendritic Cells - immunology; Humans; Kidney - immunology; Lupus nephritis; Lupus Nephritis - etiology; Lupus Nephritis - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred MRL lpr; RNA, Messenger - analysis; Dendritic cell; C1q; Complement; Lupus nephritis
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2010.02.006

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.