Epigenetic analysis of selective control of IL-17 production, and search for new strategy to treat chronic inflammation in collagen-diseases.

• Project/Area Number: 26670476
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyoto University
• Principal Investigator: Usui Takashi 京都大学, 医学(系)研究科(研究院), その他 (90362483)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: GM-CSF / IL-17 / エピゲノム制御 / ヘルパーT細胞 / 間質性肺炎 / サイトカイン

Outline of Final Research Achievements

IL-17 and the GM-CSF are important cytokines to maintain chronic inflammation of collagen diseases. In this project, we analyzed the mechanisms of production in-vitro and the treatment/intervention effects in-vivo of these cytokines.First, we established murine T cell clones which produce large amount of IL-17, and non-producer clones also. We found that gene-X controlled it through the methylation of the GC island of the IL-17 promoter domain. Second, we analyzed function of IL-17- and GM-CSF-producing cells using chronic/progressive interstitial pneumonitis model (SKG+zaymosan). We found the contribution of IL-17 was relatively low and GM-CSF was essential of this model. These findings suggest the new strategies to treat human collagen diseases which are un-met.

Research Products

• [Journal Article] Cellularity of Thymic Epithelial Cells in the Postnatal Mouse. (2018)
  • Author(s): Abe Y, Kamachi F, Kawamoto T, Makino F, Ito J, Kojima Y, Moustapha Ael D, Usui Y, Yagita H, Takasaki Y, Okumura K, Akiba H.
  • Journal Title: The Journal of Immunology Volume: 191 Pages: 1382-1388
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A novel splice variant of human L-selectin encodes a soluble molecule that is elevated in serum of patients with rheumatic diseases (2015)
  • Author(s): Hirata T, Usui T, Kobayashi S, Mimori T
  • Journal Title: Biochem Biophys Res Commun Volume: 462 Pages: 371-377
  • DOI: 10.1016/j.bbrc.2015.05.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional engraftment of human peripheral T and B cells and sustained production of autoantibodies in NOD/LtSzscid/IL-2Rγ(-/-) mice (2015)
  • Author(s): Ishikawa Y, Usui T, Shiomi A, Shimizu M, Murakami K, Mimori T
  • Journal Title: Eur J Immunol Volume: 44(11) Pages: 3453-3463
  • DOI: 10.1002/eji.201444729
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pivotal roles of GM-CSF in autoimmunity and inflammation. (2015)
  • Author(s): Shiomi A, Usui T.
  • Journal Title: Mediators Inflamm Volume: 0 Pages: 0-0
  • DOI: 10.1155/2015/568543
  • NAID: 120005745654
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] GM-CSF but not IL-17 is critical for the development of severe interstitial lung disease in SKG mice. (2014)
  • Author(s): Shiomi A, Usui T, Ishikawa Y, Shimizu M, Murakami K, Mimori T
  • Journal Title: J Immunol. Volume: 193(2) Pages: 849-59
  • DOI: 10.4049/jimmunol.1303255
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] GM-CSFと自己免疫疾患：関節炎合併間質性肺炎モデルを中心に (2015)
  • Author(s): 塩見 葵，臼井 宗，三森 経世
  • Organizer: 第36回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-21
  • Invited