A study on the pathogenesis and possible therapeutic targets of allergy march models induced by environmental factors

• Project/Area Number: 26860759
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: Kamijo Seiji 順天堂大学, 医学(系)研究科(研究院), 助教 (00445470)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アレルギーマーチ / アレルゲン / アレルギー性皮膚炎症 / アレルギー性気道炎症 / マウスモデル / アレルギー・マーチ

Outline of Final Research Achievements

We analyzed an allergy march model in which allergic airway responses to intranasally administered papain are enhanced by prior subcutaneous/epicutaneous exposure to papain. We demonstrated the involvement of basophils and mast cells in the antibody response and allergic skin inflammation in response to subcutaneous papain administration. We found that in contrast to the papain-induced airway inflammation model, in which IL-33 and ILC2s play the central roles, IL-33-induced ILC2 activation is suppressed by a papain-inducible, skin-derived suppressive factor in the papain-induced skin inflammation model. We also reported that basophil IL-4 production in response to various allergens is dependent on FceRI γ-chain.

Research Products

• [Journal Article] Airway inflammation after epicutaneous sensitization of mice requires protease activity of low-dose allergen inhalation. (2018)
  • Author(s): Nishioka I, Takai T, Maruyama N, Kamijo S, Suchiva P, Suzuki M, Kunimine S, Ochi H, Shimura S, Sudo K, Ogawa H, Okumura K, Ikeda S.
  • Journal Title: J Allergy Clin Immunol Volume: 印刷中 Issue: 6 Pages: 2271-2273
  • DOI: 10.1016/j.jaci.2017.11.035
  • Peer Reviewed
• [Journal Article] Skin treatment with detergent promotes protease allergen-dependent epicutaneous sensitization in a manner different from tape stripping in mice (2017)
  • Author(s): Ochi H, Takai T, Shimura S, Maruyama N, Nishioka I, Kamijo S, Iida H, Nakae S, Ogawa H, Okumura K, Ikeda S
  • Journal Title: J Invest Dermatol Volume: 掲載確定 Issue: 7 Pages: 1578-1582
  • DOI: 10.1016/j.jid.2017.02.970
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Subcutaneous Allergic Sensitization to Protease Allergen Is Dependent on Mast Cells but Not IL-33: Distinct Mechanisms between Subcutaneous and Intranasal Routes (2016)
  • Author(s): Kamijo S, Suzuki M, Hara M, Shimura S, Ochi H, Maruyama N, Matsuda A, Saito H, Nakae S, Suto H, Ichikawa S, Ikeda S, Ogawa H, Okumura K, Takai T.
  • Journal Title: J Immunol Volume: 196 Issue: 9 Pages: 3559-3569
  • DOI: 10.4049/jimmunol.1500717
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Epicutaneous allergic sensitization by cooperation between allergn protease activity and mechanical skin barrier damage in mice (2016)
  • Author(s): Shimura S, Takai T, Iida H, Maruyama N, Ochi H, Kamijo S, Nishioka I, Hara M, Matsuda A, Saito H, Nakae S, Ogawa H, Okumura K, Ikeda S.
  • Journal Title: J Invest Dermatol Volume: 136 Issue: 7 Pages: 1408-1417
  • DOI: 10.1016/j.jid.2016.02.810
  • Peer Reviewed
• [Journal Article] Innate basophil IL-4 responses against allergens, endotoxin, and cytokines require the Fc receptor γ-chain. (2016)
  • Author(s): Kamijo S, Nunomura S, Ra C, Kanaguchi Y, Suzuki Y, Ogawa H, Okumura K, Takai T.
  • Journal Title: J Allergy Clin Immunol Volume: 137 Issue: 5 Pages: 1613-1615
  • DOI: 10.1016/j.jaci.2015.10.037
  • Peer Reviewed
• [Journal Article] Presensitization to Ascaris antigens promotes induction of mite-specific IgE upon mite antigen inhalation in mice (2016)
  • Author(s): Suzuki M, Hara M, Ichikawa S, Kamijo S, Nakazawa T, Hatanaka H, Akiyama K, Ogawa H, Okumura K, Takai T
  • Journal Title: Allergology International Volume: 65 Issue: 1 Pages: 44-51
  • DOI: 10.1016/j.alit.2015.07.003
  • NAID: 130005290333
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Epicutaneous Administration of Papain Induces IgE and IgG Responses in a Cysteine Protease Activity-Dependent Manner (2014)
  • Author(s): Iida H, Takai T, Hirasawa Y, Kamijo S, Shimura S, Ochi H, Nishioka I, Maruyama N, Ogawa H, Okumura K, Ikeda S
  • Journal Title: Allergology International Volume: 63 Issue: 2 Pages: 219-226
  • DOI: 10.2332/allergolint.13-OA-0621
  • NAID: 130004477213
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TSLP expression induced via Toll-like receptor pathways in human keratinocytes (2014)
  • Author(s): Takai T, Chen X, Xie Y, Vu AT, Le TA, Kinoshita H, Kawasaki J, Kamijo S, Hara M, Ushio H, Baba T, Hiramatsu K, Ikeda S, Ogawa H, Okumura K
  • Journal Title: Methods Enzymol Volume: 535 Pages: 371-387
  • DOI: 10.1016/b978-0-12-397925-4.00021-3
  • Peer Reviewed
• [Presentation] Protease allergen-induced local IL-17A production in skin tissue and accumulation of IL-17A+ γδ T cells in skin draining lymph nodes; possible contribution to enhancement of skin eosinophilia and serum IgE response. (2017)
  • Author(s): KAMIJO Seiji, NAKAE Susumu, OGAWA Hideoki, OKUMURA Ko, TAKAI Toshiro
  • Organizer: 日本免疫学会総会・学術集会
• [Presentation] Contribution of IL-17A to papain-induced allergic responses in the skin and production of IL-17A from dendritic epidermal T cells in the papain-exposed skin (2016)
  • Author(s): KAMIJO Seiji, NAKAE Susumu, OGAWA Hideoki, OKUMURA Ko, TAKAI Toshiro
  • Organizer: 第45回日本免疫学会総会・学術集会
  • Place of Presentation: 沖縄コンベンションセンター・ラグナガーデンホテル
  • Year and Date: 2016-12-05
• [Presentation] アレルゲン、LPSおよびサイトカイン刺激による好塩基球のIL-4 産生はFc受容体g鎖に依存する (2016)
  • Author(s): 上條 清嗣，布村 聡，羅 智靖，金口 泰彦，鈴木 祐介，小川 秀興，奥村 康，高井 敏朗
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2016-06-17
• [Presentation] Subcutaneous allergic sensitization to protease allergen is dependent on mast cells but not IL-33: Distinct mechanisms between subcutaneous and intranasal routes (2015)
  • Author(s): KAMIJO Seiji, TAKAI Toshiro, HARA Mutsuko, MATSUDA Hironori, MATSUDA Akira, SAITO Hirohisa, NAKAE Susumu, ICHIKAWA Saori, OGAWA Hideoki, OKUMURA Ko
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Year and Date: 2015-11-18
• [Presentation] Distinct Mechanisms for Allergic Sensitization to Protease Allergen between Subcutaneous and Intranasal Routes (2014)
  • Author(s): Seiji Kamijo, Toshiro Takai, Mutsuko Hara, Hironori Matsuda, Akira Matsuda, Hirohisa Saito, Susumu Nakae, Saori Ichikawa, Hideoki Ogawa, Ko Okumura
  • Organizer: 第４３回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] プロテアーゼアレルゲンによるIgE産生と気道炎症の誘導 (2014)
  • Author(s): 上條清嗣、高井敏朗、中江進、斉藤博久、奥村康
  • Organizer: 第２６回日本アレルギー学会春季臨床大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-05-09 – 2014-05-11
  • Invited
• [Book] 医学の歩み (2014)
  • Author(s): 高井敏朗、上條清嗣
  • Total Pages: 61
  • Publisher: 医歯薬出版株式会社