Establishing a murine model of cutaneous adverse drug reaction

• Project/Area Number: 25461691
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Osaka University
• Principal Investigator: Azukizawa Hiroaki 大阪大学, 医学(系)研究科(研究院), 招へい教員 (10379240)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 薬疹 / 動物モデル / Stevens-Johnson症候群 / 中毒性表皮壊死症 / 薬剤性過敏症症候群 / T細胞 / ペプチド / インターフェロン

Outline of Final Research Achievements

In mice, it is difficult to induce rash or drug eruption by administration of certain drugs in vivo. Here, we studied in vitro screening of mouse drug reactive T cells isolated from either T cell receptor (TCR) transgenic mice or wild-type mice to find candidate drugs for establishing animal model of drug eruption using drugs. OT-I TCR transgenic mice and wild type mice were used for this study. When enriched CD8+ T cells from OT-I mice were stimulated with SIINFEKl peptide in the presence of autologous antigen presenting cells in vitro, IFN-gamma production was detected by intracellular staining. By using this assay, we tried to detect IFN-gamma production by either OT-I T cells or wild-type T cells after adding 150 drugs independently.

Research Products

• [Journal Article] B-1 B cell progenitors transiently and partially express keratin 5 during differentiation in bone marrow. (2016)
  • Author(s): Hanafusa T, Kato K, Azukizawa H, Miyazaki J, Takeda J, Katayama I.
  • Journal Title: J Dermatol Sci. Volume: 81(3) Issue: 3 Pages: 173-81
  • DOI: 10.1016/j.jdermsci.2015.11.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch. (2015)
  • Author(s): Hirobe S, Azukizawa H, Hanafusa T, Matsuo K, Quan YS, Kamiyama F, Katayama I, Okada N, Nakagawa S.
  • Journal Title: Biomaterials. Volume: 57 Pages: 50-8
  • DOI: 10.1016/j.biomaterials.2015.04.007
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of additional i.v. immunoglobulin to steroid therapy in Stevens-Johnson syndrome and toxic epidermal necrolysis. (2015)
  • Author(s): Aihara M, Kano Y, Fujita H, Kambara T, Matsukura S, Katayama I, Azukizawa H, Miyachi Y, Endo Y, Asada H, Miyagawa F, Morita E, Kaneko S, Abe R, Ochiai T, Sueki H, Watanabe H, Nagao K, Aoyama Y, Sayama K, Hashimoto K, Shiohara T; SJS/TEN Study Group.
  • Journal Title: J Dermatol Volume: 42 Issue: 8 Pages: 768-777
  • DOI: 10.1111/1346-8138.12925
  • Peer Reviewed / Open Access
• [Journal Article] Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: Survey conducted by the Asian Research Committee on Severe Cutaneous Adverse Reactions (ASCAR) (2015)
  • Author(s): Kano Y, Tohyama M, Aihara M, Matsukura S, Watanabe H, Sueki H, Iijima M, Morita E, Niihara H, Asada H, Kabashima K, Azukizawa H, Hashizume H, Nagao K, Takahashi H, Abe R, Sotozono C, Kurosawa M, Aoyama Y, Chu CY, Chung WH, Shiohara T
  • Journal Title: Journal of Dermatology Volume: 42 Issue: 3 Pages: 276-282
  • DOI: 10.1111/1346-8138.12770
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genetic variants associated with phenytoin-related severe cutaneous adverse reactions (2014)
  • Author(s): Chung WH, Chang WC, Lee YS, Wu YY, Yang CH, Ho HC, Chen MJ, Lin JY, Hui RC, Ho JC, Wu WM, Chen TJ, Wu T, Wu YR, Hsih MS, Tu PH, Chang CN, Hsu CN, Wu TL, Choon SE, Hsu CK, Chen DY, Liu CS, Lin CY, Kaniwa N, Saito Y, Takahashi Y, Nakamura R, et al.
  • Journal Title: JAMA Volume: 312 Issue: 5 Pages: 525
  • DOI: 10.1001/jama.2014.7859
  • URL: https://pure.teikyo.jp/en/publications/72f85e5d-0e6f-4211-8c2c-a32770607856
  • Peer Reviewed / Open Access
• [Journal Article] 【薬物アレルギー-疑うべきポイントと対処法】 薬物アレルギーの発症機序 (2014)
  • Author(s): 小豆澤 宏明
  • Journal Title: 薬事 Volume: 56（14） Pages: 2135-2140
• [Journal Article] 【重症薬疹の診断と治療 アップデート】 重症薬疹の検査 (2014)
  • Author(s): 小豆澤 宏明
  • Journal Title: アレルギー・免疫 Volume: 21（8） Pages: 1240-1246
• [Journal Article] 重症薬疹の診断と治療】 薬疹におけるリンパ球刺激試験でとらえる薬剤特異的T細胞 (2013)
  • Author(s): 小豆澤 宏明
  • Journal Title: 臨床免疫・アレルギー科 Volume: 59巻4号 Pages: 438-444
  • Peer Reviewed
• [Journal Article] 【薬疹を診る-注意点とその対応】最近の薬疹 注意すべき薬剤とその臨床症状 (2013)
  • Author(s): 小豆澤 宏明
  • Journal Title: 日本医師会雑誌 Volume: 142巻3号 Pages: 503-507
  • Peer Reviewed
• [Journal Article] Barrier abnormality due to ceramide deficiency leads to psoriasiform inflammation in a mouse model. (2013)
  • Author(s): Nakajima K, Terao M, Takaishi M, Kataoka S, Goto-Inoue N, Setou M, Horie K, Sakamoto F, Ito M, Azukizawa H, Kitaba S, Murota H, Itami S, Katayama I, Takeda J, Sano S.
  • Journal Title: J Invest Dermatol. Volume: 133(11) Pages: 2555-65
  • Peer Reviewed
• [Journal Article] Development and clinical study of a self-dissolving microneedle patch for transcutaneous immunization device. (2013)
  • Author(s): Hirobe S, Azukizawa H, Matsuo K, Zhai Y, Quan YS, Kamiyama F, Suzuki H, Katayama I, Okada N, Nakagawa S.
  • Journal Title: Pharm Res. Volume: 30(10) Pages: 2664-74
  • Peer Reviewed
• [Presentation] UVBからUVA領域で紅斑反応を認めたアミオダロンによる光線過敏症の１例 (2015)
  • Author(s): 加藤健一,小豆澤 宏明,片山 一朗
  • Organizer: 日本皮膚アレルギー・接触皮膚炎学会総会
  • Place of Presentation: 松江
  • Year and Date: 2015-11-20
• [Presentation] In vitro screening of drug-reactive T cells in mice (2014)
  • Author(s): Kenichi Kato, Hiroaki Azukizawa, Takaaki Hanafusa, Ichiro Katayama
  • Organizer: the 39th Annual Meeting of Japanese Society of Investigative Dermatology
  • Place of Presentation: 吹田
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Analysis of B cell subsets in severe cutaneous adverse reaction (2014)
  • Author(s): Hiroaki Azukizawa, Kenichi Kato, Ichiro Katayama
  • Organizer: The 6th Drug Hypersensitivity Meeting.
  • Place of Presentation: Bern Switzerland
  • Year and Date: 2014-04-09 – 2014-04-12
• [Presentation] 抗TNF-α阻害薬投与後に発症した、thymoma non-associated multiorgan autoimmunityの一例 (2013)
  • Author(s): 井上 知子, 花房 崇明, 小豆澤 宏明, 横見 明典, 片山 一朗
  • Organizer: 第112回日本皮膚科学会総会
  • Place of Presentation: 横浜
• [Presentation] A case of TEN induced by aspirine (2013)
  • Author(s): Hiroaki Azukizawa
  • Organizer: World SCAR joint meeting
  • Place of Presentation: Keelung, Taiwan
• [Presentation] Lymphocyte transformation test demonstrated by flow cytometry. (2013)
  • Author(s): Hiroaki Azukizawa
  • Organizer: The 8th International Congress of Cutaneous Adverse Reactions.
  • Place of Presentation: Chang Gung University, Taiwan
  • Invited