Elucidation of the mechanisms by which an inhibitory receptor regulates the development of autoimmune subepidermal bullous diseases
Project/Area Number |
19K08782
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53050:Dermatology-related
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Research Institution | Juntendo University |
Principal Investigator |
Izawa Kumi 順天堂大学, 大学院医学研究科, 特任准教授 (80708313)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 抑制型受容体 / 好中球 / 免疫複合体 / 抑制型免疫受容体 / 自己免疫性水疱症 / 天疱瘡 / ペア型レセプター / CD300 / 自己免疫性表皮下水疱症 / セラミド |
Outline of Research at the Start |
自己免疫性水疱症は表皮の自己抗原に対する自己抗体が原因となる難治性皮膚疾患である。免疫複合体が好中球などのミエロイド系細胞を活性化させて病態を形成する。他方、免疫複合体によるミエロイド系細胞の活性化と自己免疫性水疱症の病態はどのように制御されるかを明らかにすることを目標とする。ミエロイド系細胞のCD300fに着目して自己免疫性水疱症の疾患モデルを解析し、免疫複合体によるミエロイド系細胞の活性化と自己免疫性水疱症の制御メカニズムを解明を目指す。最終的な目標は自己免疫性水疱症に対してセラミドvesicleを利用するCD300f標的療法の有効性を検証して治療法を確立することである。
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Outline of Final Research Achievements |
Bullous pemphigoid, which is caused by autoantibody to type XVII collagen (COL17), and epidermolysis bullosa acquisita, which is caused by autoantibody to type VII collagen (COL7), are autoimmune subepidermal bullous diseases. We administered antibody to COL17 or COL7 to mice, that induced bullous pemphigoid or epidermolysis bullosa acquisita, respectively, in mice. As compared to wild type mice, neutrophil-deficient mice exhibited the decline in clinical scores and the reduction of inflammatory cell infiltration in skin in these models, indicating that neutrophil activation is responsible for the development of these diseases. On the other hand, CD300f deficiency did not significantly the severity of these diseases in mice. These results suggested that CD300f failed to regulate the activation of neutrophils by immune complexes in these models.
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Academic Significance and Societal Importance of the Research Achievements |
マウスモデルの解析により、表皮下水疱症の病態形成に好中球の活性化が重要であることが確認された。一方、表皮下水疱症モデルにおいて、抑制型受容体CD300fは免疫複合体による好中球の活性化を抑制しないこと、CD300fは表皮下水疱症の治療標的として不適であることが判明した。本研究成果は、免疫複合体による好中球の活性化を強く抑制する治療法を開発するための基礎となるので、その学術的意義や社会的意義が存在すると考えられる。
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Report
(5 results)
Research Products
(79 results)
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[Journal Article] The protective role of conjunctival goblet cell mucin sialylation2023
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.
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Journal Title
Nat Commun
Volume: 14
Issue: 1
Pages: 1417-1417
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
J Immunol.
Volume: -
Issue: 12
Pages: 3098-3106
DOI
Related Report
Peer Reviewed
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[Journal Article] Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice2021
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.
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Journal Title
Ocul Surf.
Volume: 22
Pages: 153-162
DOI
Related Report
Peer Reviewed
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[Journal Article] Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy.2021
Author(s)
Takasato Y, Kurashima Y, Kiuchi M, Hirahara K, Murasaki S, Arai F, Izawa K, Kaitani A, Shimada k, Saito Y, Toyoshima S, Nakamura M, Fujisawa K, Okayama Y, Kunisawa J, Kubo M, Takemura N, Uematsu S, Akira S, Kitaura J, Takahashi T, Nakayama T, Kiyono H
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Journal Title
Mucosal Immunol
Volume: 14
Issue: 3
Pages: 640-651
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[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 T, Maehara A, Nagamine M, Yamada H, Ando T, Ide T, Matsuzawa M, Okamoto Y, Yin E, Fukase S, Wang H, Kamei A, Uchida S, Keiko M, Nakano N, Uchida K, Tamura N, Ikeda K, Ebihara N, Shimizu T, Voehringer D, Roers A, Ogawa H, Okumura K, Kitaura J
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Journal Title
J Invest Dermatol.
Volume: 140
Pages: 710-713
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] CD300f is a potential therapeutic target for the treatment of food allergy2019
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
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Journal Title
Allergy
Volume: 75
Issue: 2
Pages: 471-474
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] シアル化ムチンのヒト杯細胞における発現とアレルゲン粒子に対するゲル被膜作用2022
Author(s)
松澤萌, 安藤智暁, 深瀬紗綾, 木村芽以子, 久米泰治, 伊沢久未, 前原明絵, 中野信浩, 松田彰, 奥村康, 村上 晶, 北浦次郎, 海老原伸行
Organizer
第126回眼科学会総会
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[Presentation] アレルギー性結膜炎発症における花粉の殻刺激によるGAP形成の役割2022
Author(s)
木村芽以子, 安藤智暁, 深瀬紗綾, 松澤萌, 久米泰治, 伊沢久未, 貝谷綾子, 亀井杏奈, 前田啓子, 奥村康, 村上晶, 北浦次郎, 海老原伸行
Organizer
第126回眼科学会総会
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[Presentation] Pollen shells promote development of allergic conjunctivitis through inducible goblet cell-associated antigen passage2022
Author(s)
Meiko Kimura, Tomoaki Ando, Saaya Fukase, Moe Matsuzawa, Yasuharu Kume, Kumi Izawa, Ayako Kaitani, Nobuhiro Nakano, Keiko Maeda, Ko Okumura, Akira Murakami, Nobuyuki Ebihara, Jiro Kitaura
Organizer
第71回日本アレルギー学会学術大会
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[Presentation] シアル化ムチンのヒト杯細胞における発現の変化とアレルゲン粒子からの保護作用2022
Author(s)
松澤萌, 安藤智暁, 深瀬紗綾, 木村芽以子,久米泰治,伊沢久未, 貝谷綾子, 中野信浩, 前田啓子, 奥村康, 松田 彰, 村上晶, 海老原伸行, 北浦次郎
Organizer
第71回日本アレルギー学会学術大会
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[Presentation] Fab fragments against human IgE Cε2 inhibit the binding of IgE to its receptors2022
Author(s)
Hexing Wang, Tomoaki Ando, Toshiaki Maruyama, CJ Okumura, Kumi Izawa, Ayako Kaitani, Yasuharu Kume, Koji Tokushige, Nobuhiro Nakano, Keiko Maeda, Ko Okumura, Jiro Kitaura
Organizer
第51回日本免疫学会学術集会
Related Report
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[Presentation] Pollen shells promote allergic conjunctivitis through inducible goblet cell-associated antigen passage2022
Author(s)
Meiko Kimura, Tomoaki Ando, Saaya Fukase, Yasuharu Kume, Moe Matsuzawa, Kumi Izawa, Ayako Kaitani, Nobuhiro Nakano, Ko Okumura, Akira Murakami, Nobuyuki Ebihara, Jiro Kitaura
Organizer
第51回日本免疫学会学術集会
Related Report
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[Presentation] The protective function of conjunctival goblet cell mucin sialylation2022
Author(s)
Tomoaki Ando, Moe Matsuzawa,Yasuharu Kume, Saaya Fukase, Meiko Kimura, Kumi Izawa, Ayako Kaitani, Ko Okumura, Akira Matsuda, Akira Murakami, Nobuyuki Ebihara, Jiro Kitaura
Organizer
第51回日本免疫学会学術集会
Related Report
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[Presentation] Intranasal administration of ceramide liposomes inhibits ragweed pollen-induced allergic rhinitis by targeting CD300f2022
Author(s)
Ayako Kaitani, Takuma Ide, Kumi Izawa, Tomoaki Ando, Akie Maehara, Risa Yamamoto, Yasuharu Kume, Hexing Wang, Koji Tokushige, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
Organizer
第51回日本免疫学会学術集会
Related Report
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[Presentation] Development of a murine model for oral allergy syndrome to identify IgE cross-reactive pollen and food allergens2022
Author(s)
Risa Yamamoto, Anna Kamei, Kumi Izawa, Tomoaki Ando, Ayako Kaitani, Akie Maehara, Yasuharu Kume, Hexing Wang, Koji Tokushige, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
Organizer
第51回日本免疫学会学術集会
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[Presentation] A point mutation within the function-to-find domain (FIIND) of human NLRP1 causes an autoinflammatory disease involving liver fibrosis and dyskeratosis.2021
Author(s)
Akie Maehara, Taiki Ando, Kumi Izawa, Tomoaki Ando, Ayako Kaitani, Anna Kamei, Hexing Wang, Koji Tokushige, Nobuhiro Nakano, Naoto Tamura, Ko Okumura, Jiro Kitaura.
Organizer
第50回日本免疫学会学術集会
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[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
Related Report
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[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
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[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
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[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
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[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
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[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
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[Presentation] Establishment of sustained unresponsiveness to food allergens by oral immunotherapy is prevented by inhibition of Notch signaling.2020
Author(s)
Nobuhiro Nakano, Toshiyuki Yoneyama, Mutsuko Hara, Hiromichi Yamada, Kumi Izawa, Koichiro Uchida, Ayako Kaitani, Tomoaki Ando, Jiro Kitaura, Yoshikazu Ohtsuka, Toshiaki Shimizu, Hideoki Ogawa, Ko Okumura
Organizer
JSA/WAO Joint Congress 2020 (Web)(国際学会)
Related Report
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[Presentation] Differential lipid recognition by mouse versus human CD300f, inhibiting IgE- and mast cell-dependent anaphylaxis, depends on a single amino acid substitution in its immunoglobulin-like domain.2020
Author(s)
Ayako Kaitani, Kumi Izawa, Tomoaki Ando, Akie Maehara, Enzhi Yin, Moe Matsuzawa, Taiki Ando, Takuma Ide, Yoko Okamoto, Saaya Fukase, Mayuki Kojima, Anna Kamei, Hexing Wang, Ko Okumura, Jiro Kitaura
Organizer
JSA/WAO Joint Congress 2020 (Web)(国際学会)
Related Report
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[Presentation] Differential lipid recognition by mouse vs human CD300f, inhibiting IgE-mediated anaphylaxis, depends on a single amino acid substitution.2020
Author(s)
Ayako Kaitani, Kumi Izawa, Tomoaki Ando, Akie Maehara, Moe Matsuzawa, Taiki Ando, Takuma Ide, Yoko Okamoto, Saaya Fukase, Mayuki Kojima, Anna Kamei, Meiko Kimura, Hexing Wang, Ko Okumura, Jiro Kitaura
Organizer
日本研究皮膚科学会 第45回年次学術大会・総会(オンライン開催)
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[Presentation] Differential lipid recognition by mouse versus human CD300f, inhibiting IgE-mediated mast cell activation, depends on a single amino acid substitution in its immunoglobulin-like domain2019
Author(s)
Ayako Kaitani, Kumi Izawa, Tomoaki Ando, Akie Maehara, Enzhi Yin, Moe Matsuzawa, Saaya Fukase, Hexing Wang, Keiko Maeda, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
Organizer
第48回日本免疫学会
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[Presentation] Mast cell- and IgE-dependent anaphylaxis is regulated by the interaction between inhibitory LMIR3/activating LMIR7 and specific lipids2019
Author(s)
Kumi Izawa, Ayako Kaitani, Tomoaki Ando, Akie Maehara, Takuma Ide, Moe Matsuzawa, Saaya Fukase, Anna Kamei, Taiki Ando, Nobuhiro Nakano, Ko Okumura Jiro Kitaura
Organizer
第48回日本免疫学会
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[Presentation] Exaggerated inflammasome activation by a novel NLRP1 mutant derived from a rare disease with severe liver fibrosis2019
Author(s)
Taiki Ando, Akie Maehara, Tomoaki Ando, Kumi Izawa, Ayako Kaitani, Enzhi Yin, Takuma Ide, Keiko Maeda, Nobuhiro Nakano, Naoto Tamura, Ko Okumura, Jiro Kitaura
Organizer
第48回日本免疫学会
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[Presentation] Identification of inhibitory mechanisms in pseudo-allergy involving Mrgprb2/MRGPRX2-mediated mast cell activation2019
Author(s)
Yoko Okamoto, Ayako Takamori, Kumi Izawa, Tomoaki Ando, Ayako Kaitani, Akie Maehara, Enzhi Yin, Hiromichi Yamada, Hexing Wang, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
Organizer
第48回日本免疫学会
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[Presentation] An inhibitory receptor CD300f inhibits the pathogenesis of OVA-induced food allergy in mice2019
Author(s)
Anna Kamei, Shino Uchida, Hiromichi Yamada, Kumi Izawa, Tomoaki Ando, Naoko Negishi, Akie Maehara, Ayako Kaitani, Yoko Okamoto, Nobuhiro Nakano, Ko Okumura, Jiro Kitaura
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第48回日本免疫学会
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