Understanding of circadian rhythm in the fish immunity

• Project/Area Number: 17K07915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Aquatic bioproduction science
• Research Institution: University of Miyazaki
• Principal Investigator: Kono Tomoya 宮崎大学, 農学部, 准教授 (60527547)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 魚類 / 免疫 / 概日リズム / 時計遺伝子 / サイトカイン / サイトカイン遺伝子 / 免疫増強

Outline of Final Research Achievements

The circadian expression of immune-related genes such as TNF-alpha, IL-1beta, CC chemokines (CCL18L, 19, 25L) and CXC chemokines (CXCL11) was revealed. In addition, it was clarified that clock gene response elements exist in the transcription regulatory regions of the said immune-related genes. Subsequently, it was revealed that the clock gene Bmal1:Clock1 heterodimer binds to the transcriptional regulatory region of TNF-alpha gene and regulates the expression. Furthermore, it was confirmed that expression of immune-related genes with circadian rhythm shown above was strongly induced by immuno-stimulation during a time zone showing the acrophase of the clock gene expression. These results suggest that circadian control exists in fish immune responses.

Academic Significance and Societal Importance of the Research Achievements

本研究で魚類の免疫リズムの一端を明らかにしたことは、魚類分野に貢献するばかりでなく、脊椎動物の免疫システムにおける多様性と画一性を解き明かす鍵となり、進化生物学や比較免疫学の発展に寄与するものである。さらに、研究より見出された「異なる時間帯での免疫刺激は、その後誘導される免疫応答に違いをもたらす」という知見は、水産増養殖現場で免疫賦活剤を使用する際の投与タイミングの重要性を示唆しており、将来的には疾病対策の効果改善に大きく寄与するものとなる。

Research Products

• [Journal Article] Circadian oscilattion of TNF-alpha gene expression regulated by clock gene, BMAL1 and CLOCK1 in the Japanese medaka (Oryzias latipes) (2019)
  • Author(s): Teika Onoue, Goshi Nishi, Jun-ichi Hikima, Masahiro Sakai and Tomoya Kono
  • Journal Title: International Immunopharmacology Volume: 70 Pages: 362-371
  • DOI: 10.1016/j.intimp.2019.02.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification and immunoregulatory function of neuromedin U (NMU) in the Japanese pufferfish Takifugu rubripes (2017)
  • Author(s): Tomoya Kono, Takanori Ida, Natsumi Kawahara, Fumiya Watanabe, Gouranga Biswas, Takahiro Sato, Kenji Mori, Mikiya Miyazato
  • Journal Title: Developmental and Comparative Immunology Volume: in press Pages: 246-256
  • DOI: 10.1016/j.dci.2017.03.007
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Diurnal variation of CC motif chemokine 13 gene regulated by clock gene in medaka (Oryzias latipes) (2019)
  • Author(s): Teika Onoue, Jun-ichi Hikima, Masahiro Sakai, Tomoya Kono
  • Organizer: Marine Biotechnology Conference 2019
  • Int'l Joint Research
• [Presentation] メダカTLR9遺伝子の概日リズム発現 (2019)
  • Author(s): 多比良元輝、尾上禎佳、引間順一、酒井正博、河野智哉
  • Organizer: 令和2年度日本水産学会春季大会
• [Presentation] メダカTNF-alpha遺伝子の日内変動 (2018)
  • Author(s): 尾上禎佳、引間順一、酒井正博、河野智哉
  • Organizer: 平成30年度日本水産学会秋季大会
• [Presentation] Circadian oscillation of bmal1 and cytokine genes in the medaka (2017)
  • Author(s): Teika Onoue, Jun-ichi Hikima, Masahiro Sakai, Tomoya Kono
  • Organizer: The Japanese Society of Fisheries Science
  • Int'l Joint Research
• [Presentation] ペプチド研究を水産養殖業に活かす (2017)
  • Author(s): 河野智哉
  • Organizer: 生命科学系学会合同年次大会
  • Invited