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• W4289538420 abstract "Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease with complex pathogenic mechanisms. Complement C1q has been shown to play a major role in SLE, and autoantibodies against C1q (anti-C1q) are strongly associated with SLE disease activity and severe lupus nephritis suggesting a pathogenic role for anti-C1q. Whereas C1q alone has anti-inflammatory effects on human monocytes and macrophages, C1q/anti-C1q complexes favor a pro-inflammatory phenotype. This study aimed to elucidate the inflammatory effects of anti-C1q on peripheral blood mononuclear cells (PBMCs).Isolated monocytes, isolated T cells and bulk PBMCs of healthy donors with or without concomitant T cell activation were exposed to C1q or complexes of C1q and SLE patient-derived anti-C1q (C1q/anti-C1q). Functional consequences of C1q/anti-C1q on cells were assessed by determining cytokine secretion, monocyte surface marker expression, T cell activation and proliferation.Exposure of isolated T cells to C1q or C1q/anti-C1q did not affect their activation and proliferation. However, unspecific T cell activation in PBMCs in the presence of C1q/anti-C1q resulted in increased TNF, IFN-γ and IL-10 secretion compared with C1q alone. Co-culture and inhibition experiments showed that the inflammatory effect of C1q/anti-C1q on PBMCs was due to a direct CD40-CD154 interaction between activated T cells and C1q/anti-C1q-primed monocytes. The CD40-mediated inflammatory reaction of monocytes involves TRAF6 and JAK3-STAT5 signalling.In conclusion, C1q/anti-C1q have a pro-inflammatory effect on monocytes that depends on T cell activation and CD40-CD154 signalling. This signalling pathway could serve as a therapeutic target for anti-C1q-mediated inflammation." @default.
• W4289538420 created "2022-08-03" @default.
• W4289538420 creator A5037871954 @default.
• W4289538420 creator A5083677037 @default.
• W4289538420 date "2022-01-01" @default.
• W4289538420 modified "2023-09-26" @default.
• W4289538420 title "<scp>Anti‐C1q</scp>autoantibodies from systemic lupus erythematosus patients enhance CD40–CD154‐mediated inflammation in peripheral blood mononuclear cells<i>in vitro</i>" @default.
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• W4289538420 doi "https://doi.org/10.1002/cti2.1408" @default.

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