Abstract:Regulation of endosomal TLR responses by the chemokine CXCL4 is implicated in inflammatory and fibrotic diseases. The current paradigm is that CXCL4 potentiates TLR responses by binding and facilitating endosomal delivery of nucleic acid TLR ligands. We report that in human monocytes/macrophages, CXCL4 initiates signaling cascades and downstream epigenomic reprogramming that change the profile of the TLR8 response by selectively and dramatically amplifying inflammatory gene transcription and IL-1beta; producti… Show more
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