Conclusion
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.
Methods
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.
Results
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.