PF4 and systemic sclerosis: In conclusion, our study reveals that differentiating monocytes undergo massive transcriptomic and epigenetic reprogramming upon CXCL4 exposure, and we propose that CXCL4 is a clinically relevant and important endogenous ligand bridging inflammation with fibrosis via trained immunity and provides a rationale for therapeutic targeting of CXCL4 in fibrotic diseases including SSc.