Pericyte MyD88 and IRAK4 control inflammatory and fibrotic responses to tissue injury

• DOI: 10.1172/jci87532
• Publication Date: 2016-11-20T23:00:26Z
• Authors: Irina A. Leaf; Shunsaku Nakagawa; Bryce G. Johnson; Jin Joo Cha; Kristen Mittelsteadt; Kevin M. Guckian; Ivan G. Gomez; William A. Altemeier; Jeremy S. Duffield
• Keywords: Pericyte; Proinflammatory cytokine; Myofibroblast

Fibrotic disease is associated with matrix deposition that results in the loss of organ function. Pericytes, precursors myofibroblasts, are a source pathological collagens and may be promising targets for treating fibrogenesis. Here, we have shown pericytes activate TLR2/4- MyD88-dependent proinflammatory program response to tissue injury. Similarly classic immune cells, NLRP3 inflammasome, leading IL-1β IL-18 secretion. Released signals through pericyte MyD88 amplify this response. Unexpectedly, found its downstream effector kinase IRAK4 intrinsically control migration conversion myofibroblasts. Specific ablation or pharmacological inhibition signaling by an inhibitor vivo protected against kidney injury profoundly attenuating injury, activation, differentiation Our data show pericytes, key regulators 2 major responses: inflammatory fibrogenic. Moreover, these findings suggest disruption pathway might potential therapeutic approach inhibit fibrogenesis promote regeneration.