. 2017 Mar 6;38(4):445–458. doi: 10.1038/aps.2016.162

Table 1. The roles of IRFs in macrophage/microglia polarization.

	Primary expression cell	Induction	Pathways involved	Roles in regulating marophages/microgla	References
IRF1	Microglia/macrophage	IFN-γ	Interact with MyD88.	Regulate TLR-mediated expression of pro-inflammatory genes.	^{66,67,68,69,70}
IRF2	Any cells	IFN-γ and virus	Compete with IRF1 for DNA binding sites.	Activator of H4 gene, VCAM-1, and TLR9 gene; augment LPS induced IL-1, IL-6, IL-12, and IFN-γ secretion; repress the transcriptional activation of the IFN-b gene.	^{71,72,73,74,75,76}
IRF3	Ependymal cells and choroid plexus	Molecules mediated by dsRNA and dsDNA	Be the crucial transcription factor in non-MyD88 pathway.	Alter the microglial activation phenotype from M1 to M2; transactivate the IFN-b, CXCL10, CCL5, ISG56, IFIT1, arginase II and RIG-Ilike eceptors gene.	^77,78
IRF4	Bone marrow-derived macrophages/microglia	Different mitogenic stimuli	Through IL-4 signaling; mediated by the transcription factor signal transducer and activator of Stat6.	Control M2 polarization; regulate MHC-II, Ciita, Cyp1b1, and Il1rn genes.	^79,80,81,82
IRF5	Microglia B cells, dendritic cells, macrophages/microglia	Type I IFN and viral infection	Decrease TLR3-, TLR4-, and TLR9-dependent induction of TNFα and I IFN.	Regulate host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and classic macrophage polarization.	^83,84
IRF7	Microglia/macrophages	Toll-like receptor 4 signaling	Suppress the activation of STAT1.	Involved in demyelination.	⁸⁵
IRF8	Microglia	Type I IFN	Activate gene expression that transforms microglia into a reactive phenotype.	Increase levels of Iba1, CD206, CD45, CD11b and F4/80 and F4/80; decrease levels of the chemokine receptors CCR2, CCR5 and CX3CR1.	^{86,87,88,90,91}