Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia
Takahiro Masuda1, Shosuke Iwamoto2, Satsuki Mikuriya2
1Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Institute of Neuropathology, University of Freiburg, Neurozentrum, Breisacherstraße 64, Freiburg 79106, Germany; Core Research for Evolution Science and Technology, Japan Science and Technology Agency, Tokyo 102-0076, Japan.
Abstract:
Interferon regulatory factor-8 (IRF8) plays a crucial role in the transformation of microglia to a reactive state by regulating the expression of various genes. In the present study, we show that IRF1 is required for IRF8-induced gene expression in microglia. Peripheral nerve injury induced IRF1 gene upregulation in the spinal microglia in an IRF8-dependent manner. IRF8 transduction in cultured microglia induced de novo gene expression of IRF1. Importantly, knockdown of the IRF1 gene in IRF8-transduced microglia prevented upregulation of interleukin-1β (IL-1β). Therefore, our findings suggest that expression of IL-1β is dependent on IRF1 in IRF8-expressing reactive microglia.
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