Molecular mechanisms of the CD69-Myl9 system in the chronic inflammation

• Project/Area Number: 17K15715
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: National Institute of Infectious Diseases (2018); Chiba University (2017)
• Principal Investigator: Hayashizaki Koji 国立感染症研究所, 真菌部, 研究員 (50779907)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: CD69-Myl9システム / 慢性炎症 / アレルギー性気道炎症 / T細胞 / Myl9 nets / MHCクラスⅡ発現細胞 / 血栓様構造体 / 感染 / 血管内腔 / 抗原提示細胞 / DSS誘導性大腸炎モデル / CD69リガンド / 気道炎症

Outline of Final Research Achievements

Asthma is induced by inflammatory cell accumulation into the lung tissues. Our previous reports showed that CD69 regulates allergic airway inflammation via its binding to the specific ligand, Myosin light chain 9/12 (Myl9/12). We named this novel system as “the CD69-Myl9 system”. Although this system may contribute to not only allergic inflammation but also other chronic inflammatory diseases such as colitis and tumor, the detailed mechanisms are still unknown. This project uncovered a part of the molecular mechanisms such as the induction of CD69 expression and Myl9 nets formation. Our data also elucidated that CD69-Myl9 system plays a critical role in the colitis. In near future, the CD69-Myl9 system could be a new therapeutic target for various inflammatory diseases.

Academic Significance and Societal Importance of the Research Achievements

アレルギー性気道炎症を含む慢性炎症性疾患は今日大きな社会的問題となっており、新規治療法の確立が急務となっている。本研究で詳細に解析を進めた新規炎症制御機構のCD69-Myl9システムは、炎症反応による組織障害によって誘導される為、炎症の遷延化を特徴とする慢性炎症性疾患の病態形成やその治療法確立において極めて価値のある研究ターゲットである。本研究成果によりシステムの誘導機構の一端を明らかにすることができ、また、アレルギー性気道炎症以外の疾患への関与と重要性を明らかにすることができ、学術的にも社会的にも有意義な成果を残すことができた。

Research Products

• [Journal Article] Crucial role for CD69 in allergic inflammatory responses: CD69-Myl9 system in the pathogenesis of airway inflammation (2017)
  • Author(s): Kimura Motoko Y.、Hayashizaki Koji、Tokoyoda Koji、Takamura Shiki、Motohashi Shinichiro、Nakayama Toshinori
  • Journal Title: Immunol. Rev. Volume: 278 Issue: 1 Pages: 87-100
  • DOI: 10.1111/imr.12559
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] CD69-Myl9 system regulates pathogenesis of inflammatory disorders. (2018)
  • Author(s): Kimura M.Y., Hayashizaki K. and Nakayama T.
  • Organizer: The 2nd Chiba University-UC San Diego Symposium "Mucosal Immunology, Allergy and Vaccine"
  • Int'l Joint Research
• [Presentation] Myosin light chain 9 and 12 are functional ligands for CD69 that regulate airway inflammation. (2018)
  • Author(s): Hayashizaki K., Kimura M.Y., Tokoyoda K. and Nakayama T.
  • Organizer: The 2nd Chiba University-UC San Diego Symposium "Mucosal Immunology, Allergy and Vaccine"
  • Int'l Joint Research
• [Presentation] Myosin light chain 9 and 12 are functional ligands for CD69 that regulate airway inflammation. (2017)
  • Author(s): Hayashizaki K., Kimura M.Y., Mita Y., Yagi R. and Nakayama T.
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Myosin light chain 9 and 12 are functional ligands for CD69 that regulate airway inflammation. (2017)
  • Author(s): Kimura M.Y., Hayashizaki K. and Nakayama T.
  • Organizer: The 5th Annual Meeting of the International Cytokine and Interferon Society 2017
  • Int'l Joint Research
• [Book] 臨床免疫・アレルギー科 = Clinical immunology & allergology (2018)
  • Author(s): 木村 元子, 林﨑 浩史, 中山 俊憲
  • Total Pages: 7
  • Publisher: 科学評論社
• [Book] 医学のあゆみ (2018)
  • Author(s): 木村 元子, 林﨑 浩史, 中山 俊憲
  • Total Pages: 5
  • Publisher: 医歯薬出版
• [Remarks] 千葉大学大学院医学研究院免疫発生学
  • URL: http://www.m.chiba-u.ac.jp/class/meneki/