Analysis of Langerhans cells inhibiting CD8 T cells in cutaneous interface dermatitis

• Project/Area Number: 15K09757
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Tsukuba
• Principal Investigator: Okiyama Naoko 筑波大学, 医学医療系, 講師 (10581308)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: ランゲルハンス細胞 / 自己免疫 / 苔癬反応 / 皮膚炎 / CD8 T細胞 / 細胞傷害性T細胞 / 移植片対宿主病 / 自己免疫性疾患

Outline of Final Research Achievements

Langerhans cells spontaneously exist in the epidermis, which is the target of autoaggressive CD8 T cells in a murine model of interface dermatitis. Depletion of Langerhans cells induced severe dermatitis accompanied by increased number of infiltrating CD8 T cells in this model. Apoptosis of specific antigen-stimulated CD8 T cells were induced and their proliferations were inhibited when co-cultured with Langerhans cells in vitro. In conclusion, Langerhans cells regulate autoimmune interface dermatitis via inhibitory effects on autoaggressive CD8 T cells.

Research Products

• [Journal Article] Blockade of granzyme B remarkably improves mucocutaneous diseases with keratinocyte death in interface dermatitis. (2018)
  • Author(s): Saito A, Okiyama N, Kubota N, Nakamura Y, Fujisawa Y, Watanabe R, Ishitsuka Y, Bleackley RC, Fujimoto M
  • Journal Title: J Invest Dermatol. Volume: 印刷中 Issue: 9 Pages: 2079-2083
  • DOI: 10.1016/j.jid.2018.03.1507
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical and histological characteristics of livedo racemosa in essential thrombocythemia: A report of two cases and review of the published works. (2017)
  • Author(s): Inoue S, Okiyama N, Okune M, Shiraki N, Kessoku R, Fujimoto M
  • Journal Title: J Dermatol. Volume: 44 Issue: 1 Pages: 84-87
  • DOI: 10.1111/1346-8138.13561
  • Peer Reviewed
• [Journal Article] Case of facial lupus erythematosus profundus with intractable ulceration successfully treated with dapsone. (2017)
  • Author(s): Saito A, Okiyama N, Saito K, Tanaka R, Maruyama H, Fujimoto M.
  • Journal Title: J Dermatol. Volume: 44(5) Issue: 5
  • DOI: 10.1111/1346-8138.13675
  • Peer Reviewed
• [Journal Article] Enzyme-linked immunosorbent assays for detection of anti-transcriptional intermediary factor-1 gamma and anti-Mi-2 autoantibodies in dermatomyositis. (2016)
  • Author(s): Fujimoto M, Murakami A, Kurei S, Okiyama N, Kawakami A, Mishima M, Sato S, Seishima M, Suda T, Mimori T, Takehara K, Kuwana M
  • Journal Title: J Dermatol Sci. Volume: 84(3) Issue: 3 Pages: 272-281
  • DOI: 10.1016/j.jdermsci.2016.09.013
  • Peer Reviewed
• [Journal Article] Recent advances in dermatomyositis-specific autoantibodies. (2016)
  • Author(s): Fujimoto M, Watanabe R, Ishitsuka Y, Okiyama N.
  • Journal Title: Curr Opin Rheumatol. Volume: 28 Issue: 6 Pages: 636-644
  • DOI: 10.1097/bor.0000000000000329
  • Peer Reviewed
• [Journal Article] Nodulocystic Basal Cell Carcinoma Arising Directly from a Seborrheic Keratosis: A Rare Case Report. (2016)
  • Author(s): Shibao K, Okiyama N, Tanaka R, Maruyama H, Fujisawa Y, Fujimoto M.
  • Journal Title: Indian J Dermatol. Volume: 61 Issue: 4 Pages: 443-445
  • DOI: 10.4103/0019-5154.185720
  • Peer Reviewed
• [Journal Article] Scleroderma-like skin changes occurring after the use of paclitaxel without any chemical solvents: a first case report. (2016)
  • Author(s): Shibao K, Okiyama N, Maruyama H, Jun-Ichi F, Fujimoto M.
  • Journal Title: Eur J Dermatol. Volume: 26 Issue: 3 Pages: 317-318
  • DOI: 10.1684/ejd.2016.2763
  • Peer Reviewed
• [Journal Article] Angioimmunoblastic T-cell lymphoma mimicking dermatomyositis. (2016)
  • Author(s): Saito K, Okiyama N, Shibao K, Maruyama H, Fujimoto M.
  • Journal Title: J Dermatol. Volume: 43 Issue: 7 Pages: 837-839
  • DOI: 10.1111/1346-8138.13299
  • Peer Reviewed
• [Journal Article] Immunoglobulin A vasculitis associated with HIV infection. (2016)
  • Author(s): Saito A, Okiyama N, Maruyama H, Fujimoto M.
  • Journal Title: J Dermatol. Volume: 43 Issue: 4 Pages: 444-445
  • DOI: 10.1111/1346-8138.13222
  • Peer Reviewed
• [Journal Article] Clinical perspectives and murine models of lichenoid tissue reaction/interface dermatitis. (2015)
  • Author(s): Okiyama N and Fujimoto M
  • Journal Title: J Dermatol Sci. Volume: 78 Issue: 3 Pages: 167-172
  • DOI: 10.1016/j.jdermsci.2015.03.001
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Interferon-γ deficiency attenuates skin fibrosis in a murine model of chronic graft-versus-host disease-like scleroderma. (2017)
  • Author(s): Akimasa Saito, Naoko Okiyama, Noriko Kubota, Manabu Fujimoto
  • Organizer: The European Society for Dermatological Research
  • Int'l Joint Research
• [Presentation] Langerhans cells regulate autoimmune CD8 T cell-mediated interface dermatitis (2016)
  • Author(s): Noriko Kubota, Naoko Okiyama, Akimasa Saito, Yosuke Ishitsuka, Rei Watanabe, Bjorrn E. Clausen, Manabu Fujimoto
  • Organizer: the Japanese Society of Investigative Dermatology
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2016-12-09
  • Int'l Joint Research
• [Presentation] Blockade of perforin prevents mucocutaneous injury in a murine model of interface dermatitis (2016)
  • Author(s): Akimasa Saito, Naoko Okiyama, Noriko Kubota, Yosuke Ishitsuka, Rei Watanabe, Manabu Fujimoto
  • Organizer: the Japanese Society of Investigative Dermatology
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2016-12-09
  • Int'l Joint Research
• [Presentation] Experimental myositis inducible with transfer of dendritic cells presenting a skeletal muscle C protein-derived CD8 epitope peptide (2015)
  • Author(s): Naoko Okiyama, Hisanori Hasegawa, Takatoku Oida, Shinya Hirata, Hiroo Yokozeki, Manabu Fujimoto, Nobuyuki Miyasaka and Hitoshi Kohsaka
  • Organizer: The 40th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2015-12-11
  • Int'l Joint Research
• [Presentation] Experimental myositis inducible with transfer of dendritic cells presenting a skeletal muscle C protein-derived CD8 epitope peptide (2015)
  • Author(s): Naoko Okiyama, Hisanori Hasegawa, Takatoku Oida, Shinya Hirata, Hiroo Yokozeki, Manabu Fujimoto, Nobuyuki Miyasaka and Hitoshi Kohsaka
  • Organizer: The 44th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18
  • Int'l Joint Research
• [Presentation] JAK阻害薬tofacitinibによるCD8T細胞制御性移植片対宿主病様皮膚粘膜症状の回復機構 (2015)
  • Author(s): 沖山奈緒子, Stephen I Katz
  • Organizer: 日本アレルギー学会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2015-05-26