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.

Infiltrating dendritic cells contribute to local synthesis of C1q in murine and human lupus nephritis / G. Castellano, L.A. Trouw, N. Fiore, M.R. Daha, F.P. Schena, C. van Kooten. - In: MOLECULAR IMMUNOLOGY. - ISSN 0161-5890. - 47:11-12(2010 Jul), pp. 2129-2137. [10.1016/j.molimm.2010.02.006]

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

G. Castellano
Primo
;
2010-07

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.
C1q; complement; dendritic cell; Lupus nephritis
Settore MED/14 - Nefrologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/908628
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