|開催日時：||2017年11月6日 15：00 ～ 16：00|
|講師：||John A Hamilton|
|所属：||University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Professor|
|演題：||A new GM-CSF-dependent pathway in inflammation|
Data from preclinical and clinical studies have demonstrated that granulocyte macrophage colony-stimulating factor (GMCSF) can function as a key proinflammatory cytokine. However, therapies that directly target GM-CSF function could lead to undesirable side effects, creating a need to delineate downstream pathways and mediators. Evidence will be provided that GM-CSF drives CCL17 production by acting through an IFN regulatory factor 4?dependent (IRF4-dependent) pathway in human monocytes, murine macrophages, and mice in vivo. In murine models of arthritis and pain, IRF4 regulated the formation of CCL17, which mediated the proinflammatory and algesic actions of GM-CSF. Mechanistically, GM-CSF upregulated IRF4 expression by enhancing JMJD3 demethylase activity. It also appears that CCL17 can have chemokine-independent functions in inflammatory arthritis and pain. These findings indicate that GM-CSF can mediate inflammation and pain by regulating IRF4-induced CCL17 production, providing insights into a pathway with potential therapeutic avenues for the treatment of inflammatory diseases and their associated pain.