Development of an in vivo screening method for mast cell activation regulation in atopic dermatitis

• Project/Area Number: 17K10253
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Juntendo University
• Principal Investigator: Ando Tomoaki 順天堂大学, 大学院医学研究科, 助教 (10724669)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アトピー性皮膚炎 / アレルギー / マスト細胞 / スクリーニング / CRISPR/Cas9 / IgE / ゲノム編集

Outline of Final Research Achievements

Mast cells are one of the cells involved in the pathogenesis of atopic dermatitis. We tried to establish the basic technologies that enables in vivo screening of proteins that affect mast cell activation using genome editing. We developed a tool to express the molecule that is required for genome editing, a method to control the protein levels of the molecule that records the activation status, and tools to associate the activation status and the targeted molecules. These tools may be applicable to other disease models and cell types.

Academic Significance and Societal Importance of the Research Achievements

アトピー性皮膚炎はかゆみを伴う慢性あるいは反復性の炎症性皮膚疾患である。近年新たな分子標的薬が開発されつつあり、アトピー性皮膚炎治療の選択肢は拡がってきているが、まだ完治に導くことはできておらず、今後も新たな治療薬の開発が求められている。本研究の成果はこのような分子標的薬の新たな標的を明らかにするための技術基盤であり、他の疾患の研究にも応用が可能である。今後実際のスクリーニング等を通じて、新規治療法の開発に役立てていきたい。

Research Products

• [Journal Article] The protective role of conjunctival goblet cell mucin sialylation (2023)
  • Author(s): Matsuzawa M, Ando T, Fukase S, Kimura M, Kume Y, Ide T, Izawa K, Kaitani A, Hara M, Nakamura E, Kamei A, Matsuda A, Nakano N, Maeda K, Tada N, Ogawa H, Okumura K, Murakami A, Ebihara N, Kitaura J.
  • Journal Title: Nat Commun Volume: 14 Issue: 1 Pages: 1417-1417
  • DOI: 10.1038/s41467-023-37101-y
  • Peer Reviewed / Open Access
• [Journal Article] Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1 (2023)
  • Author(s): Nagata Kazuki、Araumi Sanae、Ando Daisuke、Ito Naoto、Ando Miki、Ikeda Yuki、Takahashi Miki、Noguchi Sakura、Yasuda Yayoi、Nakano Nobuhiro、Ando Tomoaki、Hara Mutsuko、Yashiro Takuya、Hachisu Masakazu、Nishiyama Chiharu
  • Journal Title: International Journal of Molecular Sciences Volume: 24 Issue: 6 Pages: 5997-5997
  • DOI: 10.3390/ijms24065997
  • Peer Reviewed / Open Access
• [Journal Article] Mucosal Mast Cell-Specific Gene Expression Is Promoted by Interdependent Action of Notch and TGF-β Signaling. (2022)
  • Author(s): Nakano N, Saida K, Hara M, Izawa K, Ando T, Kaitani A, Kasakura K, Yashiro T, Nishiyama C, Ogawa H, Kitaura J, Okumura K.
  • Journal Title: J Immunol. Volume: - Issue: 12 Pages: 3098-3106
  • DOI: 10.4049/jimmunol.2100112
  • Peer Reviewed
• [Journal Article] Predictive value of 7S globulin-specific IgE in Japanese macadamia nut allergy patients. (2022)
  • Author(s): Yasudo H, Ando T, Kitaura J, Maruyama N, Narita M, Natsume O, Uneoka K, Miura K, Morita Y, Kamei A, Okamoto Y, Shirakawa S, Kitabayashi T, Kurihara K, Nogami K, Takasato Y, Nagao M, Ito K, Fujisawa T, Ebisawa M, Kawakami T, Matsumoto K, Saito H, Hasegawa S, Ohya Y.
  • Journal Title: J Allergy Clin Immunol Pract. Volume: - Issue: 5 Pages: 1389-1391.e1
  • DOI: 10.1016/j.jaip.2021.12.039
  • Peer Reviewed
• [Journal Article] Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice (2021)
  • Author(s): Fukase S, Ando T, Matsuzawa M, Kimura M, Sone Y, Izawa K, Kaitani A, Kamei A, Kojima M, Nakano N, Maeda K, Shimizu T, Ogawa H, Okumura K, Nishiyama N, Murakami A, Ebihara N, Kitaura J.
  • Journal Title: Ocul Surf. Volume: 22 Pages: 153-162
  • DOI: 10.1016/j.jtos.2021.08.009
  • Peer Reviewed
• [Journal Article] IgE-Associating Molecules and Their Effects on IgE-Dependent Mast Cell Reactions. (2021)
  • Author(s): Ando T, Kitaura J.
  • Journal Title: Cells. Volume: 10 Issue: 7 Pages: 1697-1697
  • DOI: 10.3390/cells10071697
  • Peer Reviewed / Open Access
• [Journal Article] シリーズIgE、抗IgE 抗体のメカニズム 前編 (2021)
  • Author(s): 安藤 智暁
  • Journal Title: アロスエルゴン Volume: 1(2) Pages: 233-239
• [Journal Article] シリーズIgE、抗IgE 抗体のメカニズム 後編 (2021)
  • Author(s): 安藤 智暁
  • Journal Title: アロスエルゴン Volume: 1(3) Pages: 370-379
• [Journal Article] A possible association between a novel NLRP1 mutation and an autoinflammatory disease involving liver cirrhosis (2021)
  • Author(s): Yasudo Hiroki、Ando Taiki、Maehara Akie、Ando Tomoaki、Izawa Kumi、Tanabe Atsushi、Kaitani Ayako、Nomura Shigeru、Seki Masafumi、Yoshida Kenichi、Oda Hirotsugu、Okamoto Yoko、Wang Hexing、Kamei Anna、Kojima Mayuki、Kimura Meiko、Uchida Koichiro、Nakano Nobuhiro、Kaneko Junichi、et al.
  • Journal Title: Hepatology Volume: - Issue: 4 Pages: 2296-2299
  • DOI: 10.1002/hep.31818
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Notch signaling contributes to the establishment of sustained unresponsiveness to food allergens by oral immunotherapy (2021)
  • Author(s): Yoneyama Toshiyuki、Nakano Nobuhiro、Hara Mutsuko、Yamada Hiromichi、Izawa Kumi、Uchida Koichiro、Kaitani Ayako、Ando Tomoaki、Kitaura Jiro、Ohtsuka Yoshikazu、Ogawa Hideoki、Okumura Ko、Shimizu Toshiaki
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 147 Issue: 3 Pages: 1063-1076
  • DOI: 10.1016/j.jaci.2020.07.011
  • Peer Reviewed
• [Journal Article] Differential Lipid Recognition by Mouse versus Human CD300f, Inhibiting Passive Cutaneous Anaphylaxis, Depends on a Single Amino Acid Substitution in its Immunoglobulin-Like Domain (2020)
  • Author(s): Izawa K、Kaitani A、Ando Tomoaki、Maehara A、Nagamine M、Yamada H、Ando T、Ide T、Matsuzawa M、Okamoto Y、Yin E、Fukase S、Wang H、Kamei A、Uchida S、Maeda K、Nakano N、Uchida K、Tamura N、Ikeda K、Ebihara N、Shimizu T、Voehringer D、Roers A、Ogawa H、Okumura K、Kitaura J
  • Journal Title: Journal of Investigative Dermatology Volume: 140 Issue: 3 Pages: 710-713
  • DOI: 10.1016/j.jid.2019.08.439
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD300f is a potential therapeutic target for the treatment of food allergy (2019)
  • Author(s): Uchida Shino、Izawa Kumi、Ando Tomoaki、Yamada Hiromichi、Uchida Koichiro、Negishi Naoko、Kaitani Ayako、Maehara Akie、Nagamine Masakazu、Kamei Anna、Takamori Ayako、Maeda Keiko、Nakano Nobuhiro、Shimizu Toshiaki、Ogawa Hideoki、Okumura Ko、Nagahara Akihito、Watanabe Sumio、Kitaura Jiro
  • Journal Title: Allergy Volume: 75 Issue: 2 Pages: 471-474
  • DOI: 10.1111/all.14034
  • NAID: 40022209298
  • Peer Reviewed / Open Access
• [Presentation] Staphylococcus aureus d-toxin in skin promotes the development of food allergy following epicutaneous sensitization (2021)
  • Author(s): Anna Kamei, Hiromichi Yamada, Kumi Izawa, Tomoaki Ando, Ayako Kaitani, Akie Maehara, Hexing Wang, Koji Tokushige, Shino Uchida, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] CD300f suppresses IgE- and mast cell-dependent allergic rhinitis (2021)
  • Author(s): Ayako Kaitani, Takuma Ide, Kumi Izawa, Anna Kamei, Tomoaki Ando, Akie Maehara, Hexing Wang, Koji Tokushige, Maeda Keiko, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] Physiological expression of St6galnac1 protects mice from allergic conjunctivitis (2021)
  • Author(s): Tomoaki Ando, Moe Matsuzawa, Saaya Fukase, Meiko Kimura, Kumi Izawa, Ayako Kaitani, Nobuhiro Nakano, Keiko Maeda, Ko Okumura, Akira Murakami, Nobuyuki Ebihara, Jiro Kitaura
  • Organizer: 第50回日本免疫学会学術集会
• [Presentation] 結膜におけるシアル化酵素St6galnac1の生理的発現がアレルギー性結膜炎の発症を抑制する (2021)
  • Author(s): 松澤 萌、安藤 智暁、深瀬 紗綾、木村 芽以子、伊沢 久未、貝谷 綾子、中野 信浩、前田 啓子、奥村 康、村上 晶、海老原 伸行、北浦 次郎
  • Organizer: 第70回日本アレルギー学会学術大会
• [Presentation] Pollen shells and soluble components play non-redundant roles in the development of allergic conjunctivitis (2021)
  • Author(s): Saaya Fukase, Tomoaki Ando, Moe Matsuzawa, Meiko Kimura, Kumi Izawa, Ayako Kaitani, Anna Kamei, Goukyo Ou, Nobuhiro Nakano, Ko Okumura, Akira Murakami, Nobuyuki Ebihara, Jiro Kitaura
  • Organizer: 第70回日本アレルギー学会学術大会
• [Presentation] 結膜におけるシアル化酵素の生理的発現がアレルギー性結膜炎の発症を抑制する (2021)
  • Author(s): 松澤萌, 安藤智暁, 深瀬紗綾, 木村芽以子, 伊沢久未, 貝谷綾子, 中野信浩, 前田啓子, 奥村康, 村上晶, 北浦次郎, 海老原伸行
  • Organizer: 第125回日本眼科学会総会
• [Presentation] マウス花粉性結膜炎モデルの発症における花粉の粒子性と抽出成分の重要性 (2021)
  • Author(s): 深瀬紗綾, 安藤智暁, 松澤萌, 木村芽以子, 伊沢久未, 貝谷綾子, 亀井杏菜, 王合興,中野信浩, 奥村康, 村上晶, 北浦次郎, 海老原伸行
  • Organizer: 第125回日本眼科学会総会
• [Remarks] 順天堂大学 大学院医学研究科 アトピー疾患研究センター
  • URL: https://research-center.juntendo.ac.jp/atopy_center/research/g1/