IRF8 is a critical transcription factor required for transforming microglia into a reactive phenotype after nerve injury
Sunday, Oct 14, 2012, 8:00 AM - 9:00 AM
, M. TSUDA
, R. YOSHINAGA
, H. TOZAKI-SAITOH
, K. OZATO
, T. TAMURA
, K. INOUE
Grad Sch. Pharm Sci. Kyushu univ, Fukuoka, Japan;
Program in Genomics of Differentiation, Natl. Inst. of Child Hlth. and Human Development, Natl. Inst. of Hlth., Bethesda, MD;
Dept. of Immunology, Grad. Sch. of Medicine, Yokohama City Univ., Yokohama, Japan
Microglia, the CNS immune-related cells, become activated by multiple types of damage and play essential roles in neuronal pathologies including neuropathic pain. However, how microglia transform into reactive phenotypes is poorly understood. Here, we identify interferon regulatory factor 8 (IRF8), a member of IRF family transcription factor, as a critical regulator of reactive microglia. We found that in 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). Forced IRF8 expression in primary cultures of microglia with lentiviral vectors promoted the transcription of genes associated with reactive states, in a manner that depends on its DNA binding domain. In contrast, IRF8 deficiency prevented these gene expressions in the spinal cord following PNI. Furthermore, mice lacking IRF8 exhibited a marked reduction in neuropathic pain, a common sequela of PNI, compared with wild-type mice without affecting normal pain sensitivity, and transferring IRF8-overexpressing microglia spinally to normal mice produced neuropathic pain-like behaviors. Together, our present findings suggest that IRF8 activates a program of gene expression that transforms microglia into a reactive phenotype that drives neuropathic pain.
[Authors]. [Abstract Title]. Program No. XXX.XX. 2012 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2012. Online.
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