Background Intraperitoneal injection of the natural oil pristane induces loss of immune tolerance and development of pristane-induced lupus (PIL) in susceptible mouse strains. PIL is characterised by high titres of autoantibodies, immune-complex glomerulonephritis (GN) and arthritis. The pathogenesis involves induction of apoptosis and a still unknown specific effect of pristane on CD11b+ Ly6Ch early monocytes which migrate into the peritoneum and produce type I IFN in a TLR7-dependent fashion (1). The role of complement in the pathogenesis of Systemic Lupus Erythematosus (SLE) has been investigated for years with controversial results. Recent data from human studies have shown that C1q may regulate the secretion of type I IFN by plasmacytoid dendritic cells (2, 3).
Objectives Considering the strong association between C1q deficiency and SLE, we tested whether lack of C1q would exacerbate the pristane-induced lupus-like syndrome.
Methods PIL was induced in C1qa–/– animals by intraperitoneal injection and the mice followed up to 9 months post treatment. Autoantibody production was measured by ELISA and kidney and hind paw joint samples were scored by experienced histopathologists. Peripheral blood (PB) and peritoneal lavage (PL) from pristane-injected mice were assessed by flow cytometry. Resident peritoneal macrophages were primed with pristane and cultured overnight in the presence of TLRs ligands. Cytokine production in culture supernatant was detected by ELISA kits.
Results Unexpectedly, the C1qa–/– mice showed a tendency to develop lower titres of circulating anti-snRNP antibodies and less histological evidence of arthritis compared to the wild type controls. No differences were observed in GN severity and survival rate between the complement deficient mice and wild type controls. Consistent with a less severe disease, we found that 2 weeks after the pristane injection the CD11b+ Ly6Ch monocytes were increased in the PB and decreased in the PL of the C1q-deficient mice, suggesting a defect in the peritoneal recruitment of these cells. Furthermore we observed decreased MIP-1α, MCP-1 and CXCL1/CK production by C1q-deficient pristane-primed resident peritoneal macrophages stimulated in vitro with TLR7 ligand.
Conclusions These novel data indicate that C1q deficient animals are partially resistant to PIL. The protection appears to be related to an impaired chemokine production by pristane-primed peritoneal macrophages. These data suggest that C1q and possibly other complement components are involved in the handling of pristane by phagocytic cells.
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Acknowledgements We thank the staff of the Biological Services Unit at our institution. This work was supported by the Arthritis Research UK (grant number 19334) and the Wellcome Trust (grant number 088517).
Disclosure of Interest None declared