| الوصف: |
Background In systemic sclerosis, activated macrophages having M2-like properties are believed to contribute to the fibrotic pathology by secreting profibrotic factors such as TGFβ. Certain synthetic peptides (10-12mers) studied here coopt the mechanism used by macrophages to detect bacteria by binding to certain regions of CD206, a receptor highly expressed in the M2 macrophages, and repolarise them to an M1 phenotype. Objectives We aimed to determine the macrophage activation signature in SSc, assess CD206 as a biomarker of ongoing fibrotic activity, and measure the effect of the peptides on macrophage activation and macrophage-fibroblast cross-talk. Methods: sCD206 was assayed in plasma (n=50 healthy, 50 limited SSc, 50 diffuse SSc), and suction blister fluid (BF) obtained over active lesions by ELISA. sSIGLEC (monocyte interferon signature) and IL-31 (Th2 signature) were assayed for comparison. Cell surface CD206 and DAMP receptor P2X7, were assayed by flow cytometry. The macrophage activation signature was investigated further by qPCR for inflammatory M1, as well as M2-like gene expression (IFNγ, Arg1, CD2106). Macrophage-fibroblast cross talk was assessed using media transfer following heat activation to SSc dermal fibroblasts assayed by qPCR for collagen I. The macrophage secretome was determined by Luminex and ELISA. Results CD206 was significantly elevated in SSc BF (SSc median sCD206 42, HC 31 pg/ml, p Conclusion A macrophage activation signature is identified in SSc patients, in proportion to the severity of disease. A mixed activation signature with inflammatory as well as pro-fibrotic M2-like properties is seen. RP peptides, which target the cells via CD206, reduce the activation signature and inhibit pro-fibrotic cross talk in these cells. Disclosure of Interests: Henry Lopez Shareholder of: Murigenics, Riptide Bioscience, Employee of: Pfizer, Kimti Kumar: None declared, George Martin Shareholder of: Riptide Bioscience, Jesse Jaynes Shareholder of: Riptide Bioscience, James Stanway: None declared, Bahja Ahmed Abdi: None declared, Nikita Arumalla: None declared, Sarah Karrar: None declared, Sian Morris: None declared, Christopher Denton Grant/research support from: GlaxoSmithKline, Inventiva, CSF Behring, Consultant for: Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Bayer, David Abraham: None declared, Xu Shiwen: None declared, Richard Stratton: None declared |
