Elucidation of T cell homeostasis regulated by KDEL receptor

• Project/Area Number: 15K08518
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Hokkaido University
• Principal Investigator: Kamimura Daisuke 北海道大学, 遺伝子病制御研究所, 講師 (20391922)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: T細胞 / 恒常性 / サイトカイン / 統合ストレス応答 / KDEL受容体

Outline of Final Research Achievements

This study proposed a new mechanism as a result of research using a mutant mouse line with reduced naive T cells. In addition to survival signals, this study showed that homeostasis of naive T cells requires a cellular stress resolution mechanism that involves the Kdelr1-PP1 pathway (Nat Commun 2015). Moreover, survival signals from T cell receptor positively regulate the cellular stress resolution depending on the affinity of a T cell receptor (Int Immunol 2016).

Research Products

• [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] 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] 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] ナイーブ T リンパ球の生存にはKDLER1-PP1経路を介した細胞ストレスの解消が重要である (2016)
  • Author(s): 上村大輔、村上正晃
  • Journal Title: 臨床免疫・アレルギー科 Volume: 66 Pages: 29-32
• [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] 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
• [Presentation] Kdelr1はナイーブT細胞の細胞ストレス解消に必要である (2016)
  • Author(s): 上村大輔
  • 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
• [Presentation] KDELR1 regulates integrated stress responses in naive T cells (2015)
  • Author(s): 上村大輔
  • Organizer: 日本分子生物学会年会・第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド (兵庫県、神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Strong TCR-mediated signals inhibit stress-mediated apoptosis in naive T cells (2015)
  • Author(s): 上村大輔
  • Organizer: 日本免疫学会総会
  • 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: 2015-11-18
• [Presentation] Kdel receptor regulates integrated stress response in naive T cells (2015)
  • Author(s): 上村大輔
  • Organizer: 研究所ネットワ－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
• [Presentation] KDEL receptor 1 controls the integrated stress response in naive T cells (2015)
  • Author(s): 上村大輔
  • Organizer: UCL Molecular Cell Biology Symposium 2015
  • Place of Presentation: Senate House (イギリス、ロンドン）
  • Year and Date: 2015-07-09
  • Int'l Joint Research
• [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