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Mechanistic diagram for microglial IRF5/4 activation. Upon DAMPs’ Stimulation, a Myddosome is formed in the cytoplasm to phosphorylate IRF5. P-IRF5 then translocates into the nucleus and bind to ISRE to regulate the expression of pro-inflammatory mediators. IL4 signaling, however, triggers activation of STAT6-Jmjd3-IRF4 pathway. IRF4 competes with IRF5 for MyD88 binding and the IRF5-IRF4 regulatory axis regulates microglial activation in a balanced way.
