RRC ID 34818
Author Masuda T, Tsuda M, Yoshinaga R, Tozaki-Saitoh H, Ozato K, Tamura T, Inoue K.
Title IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype.
Journal Cell Rep
Abstract Microglia become activated by multiple types of damage in the nervous system and play essential roles in neuronal pathologies. However, how microglia transform into reactive phenotypes is poorly understood. Here, we identify the transcription factor interferon regulatory factor 8 (IRF8) as a critical regulator of reactive microglia. Within the spinal cord, IRF8 expression was normally low; however, the expression was markedly upregulated in microglia, but not in neurons or astrocytes, after peripheral nerve injury (PNI). IRF8 overexpression in cultured microglia promoted the transcription of genes associated with reactive states; conversely, IRF8 deficiency prevented these gene expressions in the spinal cord following PNI. Furthermore, IRF8-deficient mice were resistant to neuropathic pain, a common sequela of PNI, and transferring IRF8-overexpressing microglia spinally to normal mice produced pain. Therefore, IRF8 may activate a program of gene expression that transforms microglia into a reactive phenotype. Our findings provide a newly observed mechanism for microglial activation.
Volume 1(4)
Pages 334-340
Published 2012-4-19
DOI 10.1016/j.celrep.2012.02.014
PII S2211-1247(12)00071-X
PMID 22832225
PMC PMC4158926
MeSH Animals Cell Proliferation Gene Expression Regulation Interferon Regulatory Factors / genetics Interferon Regulatory Factors / metabolism Interferon Regulatory Factors / physiology* Mice Mice, Inbred C57BL Microglia / metabolism Microglia / pathology Microglia / physiology* Pain / genetics Peripheral Nerve Injuries / genetics* Peripheral Nerve Injuries / pathology Phenotype Spinal Cord / metabolism Spinal Cord / pathology Transcription, Genetic
IF 8.032
Times Cited 73
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) CSII-EF-MCS (RDB04378).