The mechanisms of chronic inflammation by Gateway Reflex and inflammation amplifier

• Project/Area Number: 15H04741
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Hokkaido University
• Principal Investigator: Murakami Masaaki 北海道大学, 遺伝子病制御研究所, 教授 (00250514)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: 炎症アンプ / ゲートウェイ反射 / ストレス / 炎症 / ゲート反射 / 血液脳関門

Outline of Final Research Achievements

A correlation between pain intensity and the pathogenesis of inflammation is poorly established and still unclear. In this application, we elucidated that a pain evoked relapse of multiple sclerosis. Moreover, we revealed that brain micro-inflammation around specific vessels caused by chronic-stress could be switch to activate new neural pathway to regulate organ homeostasis. In addition, we identified positive-regulator of inflammation amplifier by genome wide screening. Among them, we focused on BCR and Rbm10, and clarified the mechanisms of inflammation amplifier.

Research Products

• [Journal Article] Recent advances in neuroimmune interactions. (2017)
  • Author(s): Murakami, M.
  • Journal Title: Clin Exp Neuroimmunol. Volume: 8 Issue: 1 Pages: 3-4
  • DOI: 10.1111/cen3.12382
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] EAE Induction by Passive Transfer of MOG-specific CD4+ T Cells. (2017)
  • Author(s): Tanaka, Y., Y. Arima, K. Higuchi, T. Ohki, M. Elfeky, M. Ota, D. Kamimura and M. Murakami.
  • Journal Title: Bio-protocol. Volume: 7(13) Issue: 13 Pages: 1-13
  • DOI: 10.21769/bioprotoc.2370
  • Peer Reviewed / Open Access
• [Journal Article] Targeting molecules involved in immune cell trafficking to the central nervous system for therapy in multiple sclerosis. (2017)
  • Author(s): Elfeky, M., D. Kamimura, Y. Arima, M. Murakami and L. Steinman.
  • Journal Title: Clin Exp Neuroimmunol. Volume: 8(3) Issue: 3 Pages: 183-191
  • DOI: 10.1111/cen3.12399
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit. (2017)
  • Author(s): Arima, Y., T. Ohki, N. Nishikawa, K. Higuchi, M. Ota, Y. Tanaka, J. Nio-Kobayashi, M. Elfeky, R. Sakai, Y. Mori, T. Kawamoto, A. Stofkova, Y. Sakashita, Y. Morimoto, M. Kuwatani, T. Iwanaga, Y. Yoshioka, N. Sakamoto, A. Yoshimura, M. Takiguchi, S. Sakoda, M. Prinz, D. Kamimura, M. Murakami.
  • Journal Title: eLife Volume: 6:e25517 Pages: 1-27
  • DOI: 10.7554/elife.25517
  • NAID: 120006360081
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The gateway reflex, a novel neuro-immune interaction for the regulation of regional vessels. (2017)
  • Author(s): Tanaka, Y., Y. Arima, D. Kamimura, and M. Murakami.
  • Journal Title: Front Immunol. Volume: 8 Pages: 1-9
  • DOI: 10.3389/fimmu.2017.01321
  • Peer Reviewed / Open Access
• [Journal Article] Rbm10 regulates inflammation development via alternative splicing of Dnmt3b. (2017)
  • Author(s): Atsumi T, Suzuki H, Jiang JJ, Okuyama Y, Nakagawa I, Ota M, Tanaka Y, Ohki T, Katsunuma K, Nakajima K, Hasegawa Y, Ohara O, Ogura H, Arima Y, Kamimura D, Murakami M.
  • Journal Title: Int Immunol. Volume: 29(12) Issue: 12 Pages: 581-591
  • DOI: 10.1093/intimm/dxx067
  • Peer Reviewed / Open Access
• [Journal Article] Gateway reflex, a new paradigm of neuro-immune interaction (2017)
  • Author(s): Ohki, T., D. Kamimura, Y. Arima, M. Murakami.
  • Journal Title: Clin Exp Neuroimmunol. Volume: 8 Issue: 1 Pages: 23-32
  • DOI: 10.1111/cen3.12378
  • NAID: 40021263574
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Gateway reflexes are stimulated by neural activations and promote the pathogenesis of multiple sclerosis models. (2017)
  • Author(s): Higuchi, K., D. Kamimura, A. Stofkova, N. Nishikawa, T. Ohki, Y. Arima, M. Murakami.
  • Journal Title: Nutrition and Lifestyle in Neurological Autoimmune Diseases. Volume: Chapter 5 Pages: 39-45
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Breakpoint cluster region-mediated inflammation is dependent on casein kinase II. (2016)
  • Author(s): Meng, J., J-J Jiang, T. Atsumi, H. Bando, Y. Okuyama, L. Sabharwal, I. Nakagawa, H. Higuchi, M. Ota, M. Okawara, R. Ishitani, O. Nureki, D. Higo, Y. Arima, H. Ogura, D. Kamimura and M. Murakami.
  • Journal Title: J Immunol. Volume: 197(8) Issue: 8 Pages: 3111-3119
  • DOI: 10.4049/jimmunol.1601082
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Control of chronic inflammation by the inflammation amplifier and gateway reflexes. (2016)
  • Author(s): Ota, M., D. Kamimura, I. Nakagawa, H. Higuchi, Y. Tanaka, M. Fujita, S. Hiratsuka, M. Okawara, K. Murakami, T. Atsumi, Y. Arima and M. Murakami.
  • Journal Title: Advances in Medicine and Biology. Volume: 104: Chapter 4 Pages: 65-86
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Strong TCR-mediated signals suppress integrated stress responses induced by KDELR1 deficiency in naive T cells. (2016)
  • Author(s): Kamimura, D. Y. Arima, M. Tsuruoka, J-J Jiang, H. Bando, J. Meng, L. Sabharwal, A. Stofkova, N. Nishikawa, K. Higuchi, H. Ogura, T. Atsumi, M. Murakami.
  • Journal Title: Int Immunol. Volume: 28(3) Issue: 3 Pages: 117-126
  • DOI: 10.1093/intimm/dxv059
  • NAID: 120005851045
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of inflammation amplifier-induced growth factor expression in the development of inflammatory diseases. (2015)
  • Author(s): Nakagawa, I., D. Kamimura, T. Atsumi, Y. Arima, M. Murakami.
  • Journal Title: Crit Rev Immunol. Volume: 35(5) Pages: 365-378
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Naive T cell homeostasis regulated by stress responses and TCR signaling. (2015)
  • Author(s): Kamimura, D., T. Atsumi, A. Stofkova, N. Nishikawa, T. Ohki, H. Suzuki, K. Katsunuma, J-J Jiang, H. Bando, J. Meng, L. Sabharwal, H. Ogura, T. Hirano, Y. Arima, M. Murakami.
  • Journal Title: Front Immunol Volume: 6
  • DOI: 10.3389/fimmu.2015.00638
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pain is an inducer for relapse in multiple sclerosis models via a regional neural signal. (2015)
  • Author(s): Arima, Y., K. Higuchi, N. Nishikawa, A. Stofkova, T Ohki, D. Kamimura, M. Murakami.
  • Journal Title: Clin Exp Neuroimmunol. Volume: 6 Issue: 4 Pages: 343-344
  • DOI: 10.1111/cen3.12250
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A pain-mediated neural signal induces relapse in murine autoimmune encephalomyelitis, a multiple sclerosis model (2015)
  • Author(s): Arima, Y., D. Kamimura, T. Atsumi, M. Harada, T. Kawamoto, N. Nishikawa, A. Stofkova1, T. Ohki, K. Higuchi, Y. Morimoto, P. Wieghofer, Y. Okada, Y. Mori, S. Sakoda, S. Saika, Y. Yoshioka, I. Komuro, T. Yamashita, T. Hirano, M. Prinz, M. Murakami.
  • Journal Title: eLife Volume: 4 Pages: 1-23
  • DOI: 10.7554/elife.08733
  • NAID: 120005757989
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of T cell- glial cell interactions in creating and amplifying Central Nervous System inflammation and Multiple Sclerosis disease symptoms. (2015)
  • Author(s): Huseby, ES., D. Kamimura, Y. Arima, CS. Parello, K. Sasaki, M. Murakami.
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 9
  • DOI: 10.3389/fncel.2015.00295
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] KDEL receptor 1 regulates T-cell homeostasis via PP1 that is a key phosphatase for ISR. (2015)
  • Author(s): Kamimura, D., K. Katsunuma, Y. Arima, T. Atsumi, J-J Jiang, H. Bando, J. Meng, L. Sabharwal, A. Stofkova, N. Nishikawa, H. Suzuki, H. Ogura, N. Ueda, M. Tsuruoka, M. Harada, J. Kobayashi, T. Hasegawa, H. Yoshida, H. Koseki, I. Miura, S. Wakana, K. Nishida, H. Kitamura, T. Fukada, T. Hirano, and M. Murakami
  • Journal Title: Nat. Commun. Volume: 6 Issue: 1 Pages: 7474-7474
  • DOI: 10.1038/ncomms8474
  • NAID: 120005647268
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Immune Cell Gateways in the CNS Regulated by Regional Neural Stimulations. (2015)
  • Author(s): Kamimura, D., A. Stofkova, N. Nishikawa, T. Atsumi, Y. Arima, M. Murakami.
  • Journal Title: Clin Exp Neuroimmunol. Volume: 印刷中 Issue: 2 Pages: 120-128
  • DOI: 10.1111/cen3.12198
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 微生物の中枢神経系への侵入経路およびその分子機構の解明 (2017)
  • Author(s): 村上正晃
  • Organizer: 公益財団法人発酵研究所 第11回助成研究報告会
• [Presentation] 新しい神経―免疫系連関のコンセプト「ゲートウェイ反射」とは？ (2017)
  • Author(s): 村上正晃
  • Organizer: 第28回日本生体防御学会学術総会
  • Invited
• [Presentation] Gateway reflexes, a new paradigm of neuro-immune crosstalk (2017)
  • Author(s): 村上正晃
  • Organizer: GI-CoRE GSQ, GSB, & IGM JOINT SYMPOSIUM: Quantum, Informatics, Biology, & Medicine
• [Presentation] ゲートウェイ反射による炎症性疾患の制御 (2017)
  • Author(s): 村上正晃
  • Organizer: 日本筋学会第3回学術集会
  • Invited
• [Presentation] 新しい神経- 免疫のクロストーク：ゲートウェイ反射による疾患抑制 (2017)
  • Author(s): 村上正晃
  • Organizer: TEN TOPICS IN RHEUMATOLOGY2017
• [Presentation] Gateway Reflex, a new paradigm of neuro-immune crosstalk (2017)
  • Author(s): 村上正晃
  • Organizer: AMED-ライプニッツ協会主催国際ワークショップ The German-Japan joint workshop on Neuroimmnology
  • Int'l Joint Research / Invited
• [Presentation] ゲートウェイ反射による慢性炎症および臓器の機能連関の制御 (2017)
  • Author(s): 村上正晃
  • Organizer: 第97回北海道医学大会病理系分科会（第50回北海道病理談話会）
  • Invited
• [Presentation] “病は気から”の分子メカニズム キラーストレスはどのようにして消化管疾患や突然死を もたらすか？ (2017)
  • Author(s): 村上正晃
  • Organizer: 第72回日本大腸肛門病学会学術集会
• [Presentation] Gateway Reflex, a New Concept of Neuroimmunology (2017)
  • Author(s): 村上正晃
  • Organizer: 第46回日本免疫学会学術集会
  • Invited
• [Presentation] Gateway Reflex, a Novel Concept of Neuro-Immune Cross Talk (2017)
  • Author(s): 村上正晃
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] Gateway Reflex, a New Concept in Neuroimmunology (2017)
  • Author(s): 村上正晃
  • Organizer: nternational Symposium on Geriatrics and Gerontology (ISGG)
  • Invited
• [Presentation] 炎症回路とゲートウェイ反射による病態の制御 (2017)
  • Author(s): 村上正晃
  • Organizer: 第1回Fibrosis
  • Place of Presentation: TKPガーデンシティPREMIUM名古屋駅前、名古屋市、愛知県
  • Invited
• [Presentation] サイトカインと神経活性化による慢性炎症の誘導機構 (2016)
  • Author(s): 村上正晃
  • Organizer: 北大・部局横断シンポジウム
  • Place of Presentation: 北海道大学 (北海道、札幌市)
  • Year and Date: 2016-03-07
  • Invited
• [Presentation] 神経による炎症の制御 －多発性硬化症モデルからわること- (2016)
  • Author(s): 村上正晃
  • Organizer: 日本神経学会北海道地方会
  • Place of Presentation: 北海道大学 (北海道、札幌市)
  • Year and Date: 2016-03-06
  • Invited
• [Presentation] 反応性関節炎における炎症回路の関与 (2016)
  • Author(s): 村上正晃
  • Organizer: インド-日本SICPシンポジウム
  • Place of Presentation: 東京AMED (東京都、千代田区）
  • Year and Date: 2016-02-25
  • Int'l Joint Research / Invited
• [Presentation] Kdelr1-PP1系のT細胞のストレス解消への役割 (2016)
  • Author(s): 村上正晃
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター、仙台市、宮城県
  • Invited
• [Presentation] ゲートウェイ反射 による神経炎症の惹起機構 (2016)
  • Author(s): 村上正晃
  • Organizer: 第1回Japanese School of Neuroimmunologyシンポジウム
  • Place of Presentation: 東京医科歯科大学、文京区、東京都
  • Invited
• [Presentation] ゲートウェイ反射、感覚神経の活性化を起点とする炎症誘導機構 (2016)
  • Author(s): 村上正晃
  • Organizer: 第20回日本神経麻酔集中治療学会
  • Place of Presentation: 北海道大学学術交流センター、札幌市、北海道
  • Invited
• [Presentation] 末梢神経を起点とする炎症の制御機構、ゲートウェイ反射 (2016)
  • Author(s): 村上正晃
  • Organizer: 第39回末梢神経を語る会
  • Place of Presentation: 広島国際会議場、広島市、広島県
  • Invited
• [Presentation] ゲートウェイ反射、局所の交感神経活性化を起点とする炎症誘導機構御 (2016)
  • Author(s): 村上正晃
  • Organizer: 日本リウマチ学会第3回ベーシックリサーチカンファレンス
  • Place of Presentation: アキバプラザ、千代田区、東京都
  • Invited
• [Presentation] ゲートウェイ反射、新しい神経-炎症のクロストーク (2015)
  • Author(s): 村上正晃
  • Organizer: 遺伝子病制御研究所共同利用共同研究集会「感染・免疫・炎症・発癌」
  • Place of Presentation: 北海道大学 (北海道、札幌市)
  • Year and Date: 2015-12-18
  • Invited
• [Presentation] 炎症回路はゲートウェイ反射の分子基盤である (2015)
  • Author(s): 村上正晃
  • Organizer: Advans研究会
  • Place of Presentation: ホテルグランドパレス (東京都、千代田区）
  • Year and Date: 2015-12-12
  • Invited
• [Presentation] ゲートウェイ反射による中枢神経系炎症の制御 (2015)
  • Author(s): 村上正晃
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートピアホテル (兵庫県、神戸市)
  • Year and Date: 2015-12-02
  • Invited
• [Presentation] Pain sensation induces relapse via the gateway reflex in EAE, a MS model (2015)
  • Author(s): 村上正晃
  • Organizer: 日本免疫学会シンポジウム
  • Place of Presentation: 札幌コンベンションセンター (北海道、札幌市)
  • Year and Date: 2015-11-19
  • Invited
• [Presentation] ゲートウェイ反射による認知症を含む中枢神経系疾患の治療の可能性 (2015)
  • Author(s): 村上正晃
  • Organizer: 第34回日本認知症学会総会
  • Place of Presentation: リンクステーションホール青森 (青森県、青森市)
  • Year and Date: 2015-10-03
  • Invited
• [Presentation] 炎症回路による慢性炎症疾患の制御 (2015)
  • Author(s): 村上正晃
  • Organizer: IL6の臨床と基礎を結ぶ会
  • Place of Presentation: 北海道大学 (北海道、札幌市)
  • Year and Date: 2015-09-14
  • Invited
• [Presentation] ゲートウェイ反射による脊髄再生の可能性 (2015)
  • Author(s): 村上正晃
  • Organizer: Walk Again 2015 in 札幌―脊髄再生シンポジウム
  • Place of Presentation: 北海道大学 (北海道、札幌市)
  • Year and Date: 2015-09-05
  • Invited
• [Presentation] ゲートウェイ反射を介する神経疾患の制御機構 (2015)
  • Author(s): 村上正晃
  • Organizer: 第3回鹿児島免疫性神経疾患研究会
  • Place of Presentation: レンブラントホテル鹿児島 (鹿児島県、鹿児島市)
  • Year and Date: 2015-08-25
  • Invited
• [Presentation] 神経刺激を介する病態の制御機構 (2015)
  • Author(s): 村上正晃
  • Organizer: 研究所ネットワーク国際シンポジウム
  • Place of Presentation: 北海道大学 (北海道、札幌市)
  • Year and Date: 2015-07-23
  • Invited
• [Presentation] 炎症回路による慢性炎症の制御 (2015)
  • Author(s): 村上正晃
  • Organizer: 日本動脈硬化学会
  • Place of Presentation: 仙台国際センター (宮城県、仙台市)
  • Year and Date: 2015-07-09
  • Invited
• [Presentation] 神経反射刺激を介する病態の制御機構 (2015)
  • Author(s): 村上正晃
  • Organizer: 非感染性疾患の病態解明と診断・治療法の開発拠点の形成
  • Place of Presentation: 自治医科大学 (栃木県、下野市)
  • Year and Date: 2015-07-06
  • Invited
• [Presentation] 中枢神経系の慢性炎症とゲートウェイ反射 (2015)
  • Author(s): 村上正晃
  • Organizer: NCNP神経免疫国際シンポジウム
  • Place of Presentation: 国立精神・神経医療研究センター (東京都、小平市）
  • Year and Date: 2015-06-10
  • Int'l Joint Research / Invited
• [Book] Multiple Sclerosis (2015)
  • Author(s): Kamimura, D., Y. Arima, T. Atsumi, J. Meng, L. Sabharwal, H. Bando, J-J. Jiang, ES. Huseby, M. Murakami.
  • Total Pages: 538
  • Publisher: Elsevier
• [Remarks] 痛みが神経の病気を悪化させることを実証
  • URL: http://www.igm.hokudai.ac.jp/neuroimmune/jpn/research/10-Pain-eLife.html
• [Remarks] Tリンパ球がストレスを解消する機構を解明
  • URL: http://www.igm.hokudai.ac.jp/neuroimmune/jpn/research/09-T-Red%20Nat%20Com.html