The development of immunosuppressive treatment to organ-specific autoantigens in autoimmune diseases induced by unknown autoantigens

• Project/Area Number: 25461499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kumamoto University
• Principal Investigator: HIRATA Shinya 熊本大学, 医学部附属病院, 助教 (60418829)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 自己免疫疾患 / 組織抗原特異的免疫抑制 / 樹状細胞 / 制御性T細胞 / 免疫制御療法 / 免疫抑制療法 / 抗原特異的免疫制御療法 / 多能性幹細胞 / 実験的自己免疫性脳脊髄炎

Outline of Final Research Achievements

It is desirable to develop a therapeutic means to down-modulate immune responses in an antigen-specific manner without causing systemic immune suppression. In the present study, we found that the severity of experimental autoimmune encephalomyelitis (EAE) induced by myelin autoantigen, myelin basic protein (MBP), was also decreased after treatment with genetically modified embryonic stem cell-derived dendritic cells (ES-DC) presenting another myelin autoantigen, myelin oligodendrocyte glycoprotein (MOG) peptide, and simultaneously expressing TRAIL (ES-DC-TRAIL/MOG). This preventive effect was related to regulatory T cells (Treg). For the treatment of organ-specific autoimmune diseases, induction of Treg reactive to the organ-specific autoantigens by the transfer of DC-presenting antigens and simultaneously overexpressing TRAIL therefore appears to be a promising strategy.

Research Products

• [Journal Article] Immunomodulatory drugs act as inhibitors of DNA methyltransferases and induce PU.1 up-regulation in myeloma cells. (2015)
  • Author(s): Endo S, Amano M, Nishimura N, Ueno N, Ueno S, Yuki H, Fujiwara S, Wada N, Hirata S, Hata H, Mitsuya H, Okuno Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 469 Issue: 2 Pages: 236-242
  • DOI: 10.1016/j.bbrc.2015.11.116
  • Peer Reviewed
• [Journal Article] Rituximab Monotherapy and Rituximab-Containing Chemotherapy Were Effective for Paraneoplastic Pemphigus Accompanying Follicular Lymphoma, but not for Subsequent Bronchiolitis Obliterans (2015)
  • Author(s): Hirano T, Higuchi Y, Yuki H, Hirata S, Nosaka K, Ishii N, Hashimoto T, Mitsuya H, Okuno Y.
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 55 Issue: 2 Pages: 83-88
  • DOI: 10.3960/jslrt.55.83
  • NAID: 130005104660
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access
• [Journal Article] Injury and subsequent regeneration of muscles activate local innate immunity to facilitate development and relapse of autoimmune myositis. (2015)
  • Author(s): Kimura, N., Hirata, S., Miyasaka, N., Kawahata, K. and Kohsaka, H.
  • Journal Title: Arthritis Rheumatol. Volume: 67 Issue: 4 Pages: 1107-1116
  • DOI: 10.1002/art.39017
  • Peer Reviewed / Open Access
• [Journal Article] Combined use of bortezomib, cyclophosphamide, and dexamethasone induces favorable hematological and organ responses in Japanese patients with amyloid light-chain amyloidosis: a single-institution retrospective study. (2015)
  • Author(s): Kikukawa Y, Yuki H, Hirata S, Ide K, Nakata H, Miyakawa T, Matsuno N, Nosaka K, Yonemura Y, Kawaguchi T, Hata H, Mitsuya H, Okuno Y.
  • Journal Title: Int J Hematol. Volume: 101 Issue: 7 Pages: 133-139
  • DOI: 10.1093/intimm/dxv001
  • Peer Reviewed / Open Access
• [Journal Article] Combined use of bortezomib, cyclophosphamide, and dexamethasone induces favorable hematological and organ responses in Japanese patients with amyloid light-chain amyloidosis: a single-institution retrospective study. (2014)
  • Author(s): Kikukawa Y, Yuki H, Hirata S, Ide K, Nakata H, Miyakawa T, Matsuno N, Nosaka K, Yonemura Y, Kawaguchi T, Hata H, Mitsuya H, Okuno Y.
  • Journal Title: International Journal of Hematology Volume: 101 Issue: 2 Pages: 133-139
  • DOI: 10.1007/s12185-014-1705-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells. (2014)
  • Author(s): 13.Suppression of Th1-mediated autoimmunity by embryonic stem cell-derived dendritic cells.da, T., Hirata, S., Takamatsu, K., Haruta, M., Tsukamoto, H., Ito, T., Uchino, M., Ando, Y., Nagafuchi, S., Nishimura, Y., Senju, S.
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e115198-e115198
  • DOI: 10.1371/journal.pone.0115198
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Abatacept may be effective and safe in patients with amyloid A amyloidosis secondary to rheumatoid arthritis. (2014)
  • Author(s): Nakamura, T., Kumon, Y., Hirata, S. and Takaoka, H.
  • Journal Title: Clin Exp Rheumatol. Volume: 32 Pages: 501-508
  • Peer Reviewed / Open Access
• [Journal Article] 抗PAD3/PAD4交叉抗体と関節リウマチの関節破壊, (2014)
  • Author(s): 平田真哉
  • Journal Title: リウマチ科 Volume: 51 Pages: 460-465
• [Journal Article] Abatacept mya be effective and safe in patients with AA amyloidosis secondary to rheumatoid arthritis (2014)
  • Author(s): Nakamura, T., Kumon, Y., Hirata, S. and Takaoka, H.
  • Journal Title: Clin Exp Rheumatol Volume: in press
  • Peer Reviewed
• [Journal Article] 抗PAD3/PAD4交叉抗体と関節リウマチの関節破壊 (2014)
  • Author(s): 平田真哉
  • Journal Title: リウマチ科 Volume: 51 Pages: 460-465
• [Journal Article] Suppression of elevations in serum C reactive protein levels by anti-IL-6 autoantibodies in two patients with severe bacterial infections (2013)
  • Author(s): Nanki T, Onoue I, Nagasaka K, Takayasu A, Ebisawa M, Hosoya T, Shirai T, Sugihara T, Hirata S, Kubota T, Harigai M, Miyasaka N
  • Journal Title: Ann. Rheum. Dis Volume: 72 Issue: 6 Pages: 1100-1102
  • DOI: 10.1136/annrheumdis-2012-202768
  • Peer Reviewed
• [Journal Article] SLEにおけるNETsとインフラマソーム活性化 (2013)
  • Author(s): 平田真哉
  • Journal Title: リウマチ科 Volume: 50 Pages: 376-381
• [Journal Article] リウマチ性疾患における間質性肺病変の多様性 (2013)
  • Author(s): 平田真哉
  • Journal Title: リウマチ科 Volume: 49 Pages: 127-132
• [Presentation] リンパ増殖性疾患の治療後に再燃した関節リウマチの治療における抗リウマチ薬の安全性 (2015)
  • Author(s): 平田真哉、宮川英子、坂田康明、藤本綾子、岩倉未香子、星乃光有
  • Organizer: 日本リウマチ学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-23
• [Presentation] Case Conference～全身の皮疹にて発症し、診断に難渋した症例～ (2015)
  • Author(s): 平田真哉
  • Organizer: 熊本リウマチ性疾患研究会
  • Place of Presentation: 熊本
  • Year and Date: 2015-02-13
  • Invited
• [Presentation] リンパ増殖性疾患の治療後に関節リウマチを再燃した4症例の解析 (2014)
  • Author(s): 平田真哉、野坂生郷、宮川英子、岩倉未香子、星乃光有、奥野豊
  • Organizer: 第58回日本リウマチ学会総会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 全身性エリテマトーデスに網膜病変を合併した3例の検討 (2014)
  • Author(s): 宮川英子、岩倉未香子、平田真哉、星乃光有
  • Organizer: 第58回日本リウマチ学会総会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 腸間膜脂肪織炎を合併した混合性結合組織病の一例 (2014)
  • Author(s): 岩倉未香子 平田真哉 宮川英子 星乃光有
  • Organizer: 第58回日本リウマチ学会総会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] APTTが基準値内でループスアンチコアグラントが陽性となる症例の検討 (2013)
  • Author(s): 平田真哉、内場光浩、宮川英子、渡邊祐子、星乃光有、満屋裕明
  • Organizer: 日本リウマチ学会学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 当院で経験したIgG4関連多臓器リンパ増殖性疾患の6症例の解析 (2013)
  • Author(s): 宮川英子、平田真哉、渡邊祐子、星乃光有、奥野豊、満屋裕明
  • Organizer: 日本リウマチ学会学術集会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 線維筋痛症・慢性疼痛に対するトラマドール塩酸塩アセトアミノフェンの効果の検討 (2013)
  • Author(s): 星乃光有、宮川英子、平田真哉
  • Organizer: 日本リウマチ学会学術集会
  • Place of Presentation: 国立京都国際会館