Department of Neuroimmunology

This is the first established “Department of Neuroimmunology” in Japan.

Prof. Suzumura is a pioneer who developed the “shaking off” method to obtain pure microglial culture (Suzumura, A., Mezitis, S. G., Gonatas, N. K., and Silberberg, D. H. (1987) J. Neuroimmunol. 15, 263-278).

The nervous system has long been considered as an immunological privileged site where the surveillance of the immune system does not reach out.  However, under certain conditions, the nervous system is no longer an immunological privileged site and a group of diseases emerges through the autoimmune mechanism, which is so-called “Neuroimmunological disease”.

We aim to study the immunological reactions in the nervous system under these special immunological conditions, elucidate the mechanism of neuroimmunological diseases and neurodegenerative diseases and develop the treatment for them.
We previously demonstrated that glial cells actively produce cytokines and form a unique cytokine-network in the central nervous systems.  We also revealed that glial cells (especially micoglia) present antigens to T cells as antigen-presenting cells and determine the differentiation of T cells.
Moreover, we demonstrated that glial cells (especially microglia) induce neurodegeneration through releasing harmful factors such as glutamate, nitric oxide, and inflammatory cytokines.

Now our aim is to elucidate the mechanism of neuroimmunological diseases and neurodegenerative diseases and to develop the treatment for them through the research on the following sub themes:

1. Development of a novel therapy against neurodegenerative diseases by modulating microglia.
2. The molecular biological research on the function of glial cells.
3. The immunological research on the interaction between glial cells and immunocytes.
4. Elucidation of the cytokine-network in the nervous systems.
5. The molecular biological research on interaction between glial cells and neurons in neurodegeneration.

Staff
Professor: SUZUMURA, Akio; MD, PhD. (suzumura@riem.nagoya-u.ac.jp)
Associate professor: MIZUNO, Tetsuya; MD, PhD. (tmizuno@riem.nagoya-u.ac.jp)
Assistant professor: TAKEUCHI, Hideyuki; MD, PhD. (htake@riem.nagoya-u.ac.jp)
Assistant professor: NODA, Mariko; PhD(Pharmacy) (noda@riem.nagoya-u.ac.jp)
Assistant professor: SONOBE, Yoshifumi; PhD. (sonobe@riem.nagoya-u.ac.jp)

Publications

2012
LI Endong, JIN Shijie, SONOBE Yoshifumi, MA Di, LI Hua, KAWANOKUCHI Jun, MIZUNO Tetsuya, SUZUMURA Akio, The Gap-junction inhibitor Carbenoxolone suppresses the differentiation of Th17 cells through inhibition of IL-23 expression in antigen presenting cells. Journal of Neuroimmunology 2012 In Press.

2011
MIZUNO Tetsuya, DOI Yukiko, MIZOGUCHI Hiroyuki, JIN Shijie, NODA Mariko, SONOBE Yoshifumi, TAKEUCHIHideyuki, SUZUMURA, Akio, Interleukin-34 selectively enhances the neuroprotective effects of microglia to attenuate oligomeric amyloid-b neurotoxicity. The American Journal of Pathology 179 2016-2027, 2011.

TAKEUCHI Hideyuki, MIZOGUCHI Hiroyuki, DOI Yukiko, NODA Mariko, LIANG Jianfeng, LI Hua, ZHOU Yan, MORI Rarami, YASUOKA Satoko, LI Endong, PARAJULI Bijay, KAWANOKUCHI Jun, SONOBE Yoshifumi, SATO Jun, YAMANAKA Koji, SOBUE Gen, MIZUNO Tetsuya, SUZUMURA Akio, Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer’s disease. PLoS ONE 6: e21108, 2011.

YASUOKA Satoko, KAWANOKUCHI Jun, PARAJULI Bijay, JIN Shijie, DOI Yukiko, NODA Mariko, SONOBE Yoshifumi, TAKEUCHI Hideyuki, MIZUNO Tetsuya, SUZUMURA Akio, Production and functions of IL-33 in the central nervous system. Brain Research 1315: 8-17, 2011.

ZHOU Yan, SONOBE Yoshifumi, AKAHORI Tomohiko, JIN Shijie, KAWANOKUCHI Jun, NODA Mariko, IWAKURA Yoichiro, MIZUNO Tetsuya, SUZUMURA Akio, IL-9 promotes Th17 cell migration into the central nervous system via CC chemokine ligand-20 produced by astrocytes. The Journal of Immunology 187: 4415-4421, 2011.

HASHIBA Naomi, NAGAYAMA Shigemi, ARAYA Shin-ichi, INADA Hiroyuki, SONOBE Yoshifumi, SUZUMURA Akio, MATSUI Makoto, Phenytoin at optimum doses ameliorates experimental autoimmune encephalomyelitis via modulation of immunoregulatory cells. Journal of Neuroimmunology 233: 112-119, 2011.

LI Hua, SONOBE Yoshifumi, TABATA Hiromitsu, LIANG Jianfeng, JIN Shijie, DOI Yukiko, KAWANOKUCHI Jun, TAKEUCHI Hideyuki, MIZUNO Tetsuya, SUZUMURA Akio, Tumor necrosis factor-a promotes granulocyte-macrophage colony-stimulating factor-stimulated microglia to differentiate into competent dendritic cell-like antigen-presenting cells. Clinical and Experimental Neuroimmunology 2: 1-11, 2011

2010
Liang Jianfeng, Takeuchi Hideyuki, Jin Shijie, Noda Mariko, Li Hua, Doi Yukiko, Kawanokuchi Jun, Sonobe Yoshifumi, Mizuno Tetsuya, Suzumura Akio, Glutamate induces neurotrophic factor production from microglia via protein kinase C pathway. Brain Research 1322: 8-23, 2010.

2009

DOI Yukiko, MIZUNO Tetsuya, MAKI Yuki, JIN Shijie, MIZOGUCHI Hiroyuki, IKEYAMA Masayoshi, DOI Minoru, MICHIKAWA Makoto, TAKEUCHI Hideyuki, SUZUMURA Akio: Microglia activated with toll-like receptor 9 ligand CpG attenuate oligomeric amyloid b neurotoxicity in vitro and in vivo models of Alzheimer's disease.  The American Journal of Pathology. 175: 2121-2131, 2009.

SONOBE Yoshifumi, TAKEUCHI Hideyuki, KATAOKA Kunio, LI Hua, JIN Shijie, MIMURO Maya, HASHIZUME Yoshio, SANO Yasuteru, KANDA Takashi, MIZUNO Tetsuya, SUZUMURA Akio: Interleukin-25 expressed by brain capillary endothelial cells maintains blood-brain barrier function in a protein kinase Cε-dependentmanner. The Journal of Biological Chemistry. 284:31834-31842, 2009.

JIN Shijie, TAKEUCHI Hideyuki, YAWATA Izumi, HARADA Yohei, SONOBE Yoshifumi, DOI Yukiko, LIANG Jianfeng, LI Hua, YASUOKA Satoko, ZHOU Yan, NODA Mariko, KAWANOKUCHI Jun, MIZUNO Tetsuya, SUZUMURA Akio: Blockade of glutamate release from microglia attenuates experimental autoimmune encephalomyelitis in mice.  Tohoku Journal of Experimental Medicine. 217: 87-92, 2009.


2008
TAKEUCHI Hideyuki, JIN Shijie, SUZUKI Hiromi, DOI Yukiko, LIANG Jianfeng, KAWANOKUCHI Jun, MIZUNO Tetsuya, SAWADA Makoto, SUZUMURA Akio: Blockade of microglial glutamate release protects against ischemic brain injury. Experimental Neurology. 214: 144-146, 2008.

YAWATA Izumi, TAKEUCHI Hideyuki, DOI Yukiko, LIANG Jianfeng, MIZUNO Tetsuya, SUZUMURA Akio: Macrophage-induced neurotoxicity is mediated by glutamate and attenuated by glutaminase inhibitors and gap junction inhibitors. Life Sciences. 82(21-22): 1111-1116, 2008.

LIANG Jianfeng, TAKEUCHI Hideyuki, DOI Yukiko, KAWANOKUCHI Jun, SONOBE Yoshifumi, JIN Shijie, YAWATA Izumi, LI Hua, YASUOKA Satoko, MIZUNO Tetsuya, SUZUMURA Akio: Excitatory amino acid transporter expression by astrocytes is neuroprotective against microglial excitotoxicity.  Brain Research. 1210: 11-19, 2008.

SONOBE Yoshifumi, LIANG Jianfeng, JIN Shijie, ZHANG Guiqin, TAKEUCHI Hideyuki, MIZUNO Tetsuya, SUZUMURA Akio: Microglia express a functional receptor for interleukin-23. Biochemical and Biophysical Research Communications. 370(1): 129-133, 2008.

WANG Jinyan, TAKEUCHI Hideyuki, SONOBE Yoshifumi, JIN Shijie, MIZUNO Tetsuya, MIYAKAWA Shin, FUJIWARA Masatoshi, NAKAMURA Yoshikazu, KATO Takuma, MURAMATSU Hisako, MURAMATSU Takashi, SUZUMURA Akio: Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population. Proceedings of the National Academy of Sciences USA 105(10): 3915-3920, 2008.

MIZUNO Tetsuya, ZHANG Guiqin, TAKEUCHI Hideyuki, KAWANOKUCHI Jun, WANG Jinyan, SONOBE Yoshifumi, JIN Shijie, TAKADA Naoki, KOMATSU Yukio, SUZUMURA Akio: Interferon-g directly induces neurotoxicity through a neuron specific, calcium- permeable complex of IFN-g receptor and AMPA GluR1 receptor.  FASEB Journal 22(6): 1797-1806, 2008.

KAWANOKUCHI Jun, SHIMIZU Kouki, NITTA Atsumi, YAMADA Kiyofumi, MIZUNO Tetsuya, TAKEUCHI Hideyuki, SUZUMURA Akio: Production and functions of IL-17 in microglia.  Journal of Neuroimmunology 194(1-2): 54-56, 2008.

FURUKAWA Keiko, AIXINJUELUO Wei, KASAMA Takeshi, OHKAWA Yuki, YOSHIHARA Michiko, OHMI Yusuke, TAJIMA Orie, SUZUMURA Akio, KITTAKA Daiji, FURUKAWA Koichi: Disruption of GM2/GD2 synthase gene resulted in overt expression of 9-O-acetyl GD3 irrespective of Tis21.  Journal of Neurochemistry 105(3): 1057-1066, 2008.

2007
JIN Shijie, KAWANOKUCHI Jun, MIZUNO Tetsuya, WANG Jinyan, SONOBE Yoshifumi, TAKEUCHI Hideyuki, SUZUMURA Akio: Interferon-beta is neuroprotective against the toxicity induced by activated microglia.  Brain Research 1179: 140-146, 2007

SONOBE Yoshifumi, JIN Shijie, WANG Jinyan, KAWANOKUCHI Jun, TAKEUCHI Hideyuki, MIZUNO Tetsuya, SUZUMURA Akio: Chronological Changes of CD4+ and CD8+ T Cell Subsets in the Experimental Autoimmune Encephalomyelitis, a Mouse Model of Multiple Sclerosis.  Tohoku Journal of Experimental Medicine 213: 329-339, 2007.

2006
SUZUMURA Akio, TAKEUCHI Hideyuki, ZHANG Guiqin, KUNO Reiko, MIZUNO Tetsuya: Role of glia-derived cytokines on neuronal degeneration and regeneration.  Annals of New York Academy of Science 1088: 219-229, 2006.

DOI Yukiko, LIANG Jianfeng, KUNO Reiko, ZHANG Guiqin, KAWANOKUCHI Jun, YAWATA Izumi, TAKEUCHI Hideyuki, MIZUNO Tetsuya, SUZUMURA Akio: The direct and indirect effects of serofendic acid on neuroprotection.  Annals of New York Academy of Science 1086: 91-103, 2006.

KUNO Reiko, YOSHIDA Yusuke, NITTA Atsumi, NABESHIMA Toshitaka, WANG Jinyan, SONOBE Yoshifumi, KAWANOKUCHI Jun, TAKEUCHI Hideyuki, MIZUNO Tetsuya, SUZUMURA Akio: The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes.  Brain Research 1116: 12-18, 2006.

KAWANOKUCHI Jun, MIZUNO Tetsuya, TAKEUCHI Hideyuki, KATO Hideki, WANG Jinyan, MITSUMA Norimasa, SUZUMURA Akio: Production of interferon-g by microglia.  Multiple Sclerosis 12: 558-564, 2006.

TAKEUCHI Hideyuki, JIN Shijie, WANG Jinyan, ZHANG Guiqin, KAWANOKUCHI Jun, KUNO Reiko, SONOBE Yoshifumi, MIZUNO Tetsuya, SUZUMURA Akio: Tumor necrosis factor-a induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner.  The Journal of Biological Chemistry 281: 21362-21368, 2006.

TAKEUCHI Hideyuki, WANG Jinyan, KAWANOKUCHI Jun, MITSUMA Norimasa, MIZUNO Tetsuya, SUZUMURA Akio: Interferon-g induces microglial activation-induced cell death: a hypothetical mechanism of relapse and remission in multiple sclerosis.  Neurobiology of Disease 22: 33-39, 2006.

2005
MIZUNO Tetsuya, KUNO Reiko, NITTA Atsumi, NABESHIMA Toshitaka, ZHANG Guiqin, KAWANOKUCHI Jun, WANG Jinyan, JIN Shijie, TAKEUCHI Hideyuki, SUZUMURA Akio: Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes.  Brain Research 1066: 78-85, 2005.

TAKEUCHI Hideyuki, MIZUNO Tetsuya, ZHANG Guiqin, WANG Jinyan, KAWANOKUCHI Jun, KUNO Reiko, SUZUMURA Akio: Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport.  The Journal of Biological Chemistry 280: 10444-10454, 2005.

JIANG Yue-Mei, YAMAMOTO Masahiko, KOBAYASHI Yasushi, YOSHIHARA Tsuyoshi, LIANG Yideng, TERAO Shinichi, TAKEUCHI Hideyuki, ISHIGAKI Shinsuke, KATSUNO Masahisa, ADACHI Hiroaki, NIWA Jun-ichi, TANAKA Fumiaki, DOYU Manabu, YOSHIDA Mari, HASHIZUME Yoshio, SOBUE Gen: Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis.  Annals of Neurology 57: 236-251, 2005.

BANNO Masahiro, MIZUNO Tetsuya, KATO Hideki, ZHANG Guiqin, KAWANOKUCHI Jun, WANG Jinyan, KUNO Reiko, JIN Shijie, TAKEUCHI Hideyuki, SUZUMURA Akio: The radical scavenger edaravone prevents oxidative neurotoxicity induced by peroxynitrite and activated microglia.  Neuropharmacology 48: 283-290, 2005.

KUNO Reiko, WANG Jinyan, KAWANOKUCHI Jun, TAKEUCHI Hideyuki, MIZUNO Tetsuya, SUZUMURA Akio: Autocrine activation of microglia by tumor necrosis factor-alpha.  Journal of Neuroimmunology 162: 89-96, 2005.

SONOBE Yoshifumi, YAWATA Izumi, KAWANOKUCHI Jun, TAKEUCHI Hideyuki, MIZUNO Tetsuya, SUZUMURA Akio: Production of IL-27 and other IL-12 family cytokines by microglia and their subpopulations.  Brain Research 1040: 202-207, 2005.

2004
KATO Hideki, ITO Atsushi, KAWANOKUCHI Jun, JIN Shijie, MIZUNO Tetsuya, OJIKA Kosei, UEDA Ryuzou, SUZUMURA Akio: Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells.  Multiple Sclerosis 10: 651-659, 2004.

MIZUNO Tetsuya, KUROTANI Tohru, KOMATSU Yukio, KAWANOKUCHI Jun, KATO Hideki, MITSUMA Norimasa, SUZUMURA Akio: Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia.  Neuropharmacology. 46: 404-411, 2004.

KAWANOKUCHI Jun, MIZUNO Tetsuya, KATO Hideki, MITSUMA Norimasa, SUZUMURA Akio: Effects of interferon-b on functions of microglia as inflammatory and antigen presenting cells in the central nervous system.  Neuropharmacology. 46: 734-742, 2004.

TAKEUCHI Hideyuki, NIWA Jun-ichi, HISHIKAWA Nozomi, ISHIGAKI Shinsuke, TANAKA Fumiaki, DOYU Manabu, SOBUE Gen: Dorfin prevents cell death by reducing mitochondrial localizing mutant superoxide dismutase 1 in a neuronal cell model of familial amyotrophic lateral sclerosis.  Journal of Neurochemistry 89: 64-72, 2004.

FENG Juan, MISU Tatsuro, FUJIHARA Kazuo, SAKODA Saburo, NAKATSUJI Yuji, FUKAURA Hikoaki, KIKUCHI Seiji, TASHIRO Kunio, SUZUMURA Akio, ISHII Naoto, SUGAMURA Kazuo, NAKASHIMA Ichiro, ITOYAMA Yasuto: Ibudilast, a nonselective phosphodiesterase inhibitor, regulates Th1/Th2 balance and NKT cell subset in multiple sclerosis.  Multiple Sclerosis 10: 494-498, 2004.

2003
SUZUMURA Akio, ITO Atsusi, MIZUNO Tetsuya: Phosphodiesterase inhibitors suppress IL-12 production with microglia and T helper 1 development. Multiple Sclerosis. 9:574-578, 2003.

MIZUNO Tetsuya, KAWANOKUCHI Jun, NUMATA Kenji, SUZUMURA Akio: Production and neuroprotective functions of fraclalkine in the central nervous system.  Brain Research. 979: 65-70, 2003.

(Update: 2011.12.6)