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IRF8 is a transcriptional determinant for microglial motility

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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.

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Acknowledgments

The authors thank Mr. Ryohei Yoshinaga and Mr. Shosuke Iwamoto for assisting with experiments and Dr. Keiko Ozato for kindly providing Irf8 −/−mice. This work was supported by grants from the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for Next Generation World-Leading Researchers (NEXT Program)” initiated by the Council for Science and Technology Policy (CSTP; M.T.) and the Ministry of Education, Culture, Sports, Science and Technology of Japan (T.M., M.T., K.I.), from the Japan Science and Technology Agency (JST) through the Core Research for Evolutional Science and Technology (CREST) program (K.I.) and by Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Competing financial interests

The authors have no competing financial interests to declare.

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Authors and Affiliations

  1. Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Takahiro Masuda, Nao Nishimoto, Daisuke Tomiyama, Tsuyoshi Matsuda, Hidetoshi Tozaki-Saitoh, Makoto Tsuda & Kazuhide Inoue

  2. Department of Immunology, Graduate School of Medicine, Yokohama City University, Yokohama, 236-0004, Japan

    Tomohiko Tamura

  3. Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo, 187-8502, Japan

    Shinichi Kohsaka

  4. Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Tokyo, 102-0076, Japan

    Takahiro Masuda, Hidetoshi Tozaki-Saitoh & Kazuhide Inoue

Authors
  1. Takahiro Masuda
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  2. Nao Nishimoto
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  3. Daisuke Tomiyama
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  6. Tomohiko Tamura
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  7. Shinichi Kohsaka
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  8. Makoto Tsuda
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  9. Kazuhide Inoue
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Corresponding authors

Correspondence to Makoto Tsuda or Kazuhide Inoue.

Additional information

Takahiro Masuda and Nao Nishimoto contributed equally to this work.

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Masuda, T., Nishimoto, N., Tomiyama, D. et al. IRF8 is a transcriptional determinant for microglial motility. Purinergic Signalling 10, 515–521 (2014). https://doi.org/10.1007/s11302-014-9413-8

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  • DOI: https://doi.org/10.1007/s11302-014-9413-8

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