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C1q Modulates the Response to TLR7 Stimulation by Pristane-Primed Macrophages: Implications for Pristane-Induced Lupus.
Carlucci, Francesco; Ishaque, Attia; Ling, Guang Sheng; Szajna, Marta; Sandison, Ann; Donatien, Philippe; Cook, H Terence; Botto, Marina.
Afiliação
  • Carlucci F; 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, Oxf
  • Ishaque A; Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom;
  • Ling GS; Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom;
  • Szajna M; Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom;
  • Sandison A; Department of Histopathology, Imperial College Healthcare National Health Service Trust, Charing Cross Hospital, London W6 8RP, United Kingdom.
  • Donatien P; Department of Histopathology, Imperial College Healthcare National Health Service Trust, Charing Cross Hospital, London W6 8RP, United Kingdom.
  • Cook HT; Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom;
  • Botto M; Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom;
J Immunol ; 196(4): 1488-94, 2016 Feb 15.
Article em En | MEDLINE | ID: mdl-26773156
ABSTRACT
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Terpenos / Complemento C1q / Macrófagos Peritoneais / Receptor 7 Toll-Like / Lúpus Eritematoso Sistêmico Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Immunol Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Terpenos / Complemento C1q / Macrófagos Peritoneais / Receptor 7 Toll-Like / Lúpus Eritematoso Sistêmico Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Immunol Ano de publicação: 2016 Tipo de documento: Article