IRF8 is a transcriptional determinant for microglial motility

Takahiro Masuda, Nao Nishimoto, Daisuke Tomiyama, Tsuyoshi Matsuda, Hidetoshi Tozaki-Saitoh, Tomohiko Tamura, Shinichi Kohsaka, Makoto Tsuda, Kazuhide Inoue

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Microglia, the resident immune cells of the central nervous system, are constitutively mobile cells that undergo rapid directional movement toward sites of tissue disruption. However, transcriptional regulatory mechanisms of microglial motility remain unknown. In the present study, we show that interferon regulatory factor-8 (IRF8) regulates microglial motility. We found that ATP and complement component, C5a, induced chemotaxis of IRF8 wild-type microglia. However, these responses were markedly suppressed in microglia lacking IRF8 (Irf8−/−). In a consistent manner, phosphorylation of Akt (which plays a crucial role in ATP-induced chemotaxis) was abolished in Irf8−/−microglia. Real-time polymerase chain reaction analysis revealed that motility-related microglial genes such as P2Y12 receptor were significantly suppressed in Irf8−/−microglia. Furthermore, Irf8−/−microglia exhibited a differential expression pattern of nucleotide-degrading enzymes compared with their wild-type counterparts. Overall, our findings suggest that IRF8 may regulate microglial motility via the control of microglial gene expression.

Original languageEnglish
Pages (from-to)515-521
Number of pages7
JournalPurinergic Signalling
Volume10
Issue number3
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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