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The complement component C1q is known to play a controversial role in the pathogenesis of systemic lupus erythematosus, but the underlying mechanisms remain poorly understood. Intraperitoneal injection of pristane induces a lupus-like syndrome whose pathogenesis implicates the secretion of type I IFN by CD11b(+) Ly6C(high) inflammatory monocytes in a TLR7-dependent fashion. C1q was also shown to influence the secretion of IFN-α. In this study, we explored whether C1q deficiency could affect pristane-induced lupus. Surprisingly, C1qa(-/-) mice developed lower titers of circulating Abs and milder arthritis compared with the controls. In keeping with the clinical scores, 2 wk after pristane injection the peritoneal recruitment of CD11b(+) Ly6C(high) inflammatory monocytes in C1qa(-/-) mice was impaired. Furthermore, C1q-deficient pristane-primed resident peritoneal macrophages secreted significantly less CCL3, CCL2, CXCL1, and IL-6 when stimulated in vitro with TLR7 ligand. Replenishing C1q in vivo during the pristane-priming phase rectified this defect. Conversely, pristane-primed macrophages from C3-deficient mice did not show impaired cytokine production. These findings demonstrate that C1q deficiency impairs the TLR7-dependent chemokine production by pristane-primed peritoneal macrophages and suggest that C1q, and not C3, is involved in the handling of pristane by phagocytic cells, which is required to trigger disease in this model.

Original publication

DOI

10.4049/jimmunol.1401009

Type

Journal article

Journal

Journal of immunology (baltimore, md. : 1950)

Publication Date

02/2016

Volume

196

Pages

1488 - 1494

Addresses

Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom; Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science, Botnar Research Centre, University of Oxford, Oxford OX3 7LD, United Kingdom; and francesco.carlucci@kennedy.ox.ac.uk.

Keywords

Monocytes, Macrophages, Peritoneal, Animals, Mice, Inbred BALB C, Arthritis, Lupus Erythematosus, Systemic, Disease Models, Animal, Terpenes, Interferon-alpha, Poly I-C, Chemokines, Autoantibodies, Interferon Inducers, Cytokines, Macrophage Activation, Complement C1q, Toll-Like Receptor 7