The roles of CRTH2 in IgE production

• Project/Area Number: 18K14603
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nakamura Tatsuro 東京大学, 大学院農学生命科学研究科(農学部), 特任講師 (80755554)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: IgE / CRTH2 / PGD2 / skin

Outline of Final Research Achievements

IgE antibody is an essential molecule for the induction of allergic diseases. We found that CRTH2, a receptor for PGD2, promotes IgE production by enhancement of dendritic cells activity and follicular T cell differentiation. Pharmacological inhibition of CRTH2 inhibits the increase of IgE level. CRTH2 inhibitor could be a target for the development of new therapeutic strategy for allergic diseases.

Academic Significance and Societal Importance of the Research Achievements

アレルギー疾患を根治に導くためにはIgE抗体産生を抑制する必要があるが、その方法は未だ確立されていない。本研究ではプロスタグランジンD2の受容体の一つであるCRTH2がIgE抗体産生を促進する分子メカニズムの一端を明らかにした。CRTH2阻害剤の新規抗アレルギー薬としての可能性を示した。

Research Products

• [Journal Article] 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid accelerates the healing of colitis by inhibiting transient receptor potential vanilloid 4-mediated signaling (2021)
  • Author(s): Koji Kobayashi, Kohei Ashina, Sandra Derouiche, Taiki Hamabata, Tatsuro Nakamura, Nanae Nagata, Shinya Takenouchi, Makoto Tominaga, and Takahisa Murata
  • Journal Title: FASEB Journal Volume: 35 Issue: 4 Pages: 21238-21248
  • DOI: 10.1096/fj.201903207rrr
  • Peer Reviewed
• [Journal Article] Urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of colitis-associated colorectal cancer in mice (2021)
  • Author(s): Miyazaki Yusuke、Nakamura Tatsuro、Takenouchi Shinya、Hayashi Akane、Omori Keisuke、Murata Takahisa
  • Journal Title: PLOS ONE Volume: 16 Issue: 1 Pages: 0245292-0245292
  • DOI: 10.1371/journal.pone.0245292
  • Peer Reviewed / Open Access
• [Journal Article] The role of prostaglandin D₂ in food allergy and its potential for new diagnosis and therapy methods (2020)
  • Author(s): Nakamura Tatsuro
  • Journal Title: Folia Pharmacologica Japonica Volume: 155 Issue: 6 Pages: 386-389
  • DOI: 10.1254/fpj.20046
  • NAID: 130007933847
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed
• [Journal Article] A mechanisms of drug resistance in tumor endothelial cells (2020)
  • Author(s): Kobayashi Yui、Nakamura Tatsuro、Miyazaki Yusuke、Omori Keisuke、Kobayashi Koji、Murata Takahisa
  • Journal Title: Folia Pharmacologica Japonica Volume: 155 Issue: 5 Pages: 351-351
  • DOI: 10.1254/fpj.20018
  • NAID: 130007894593
  • Peer Reviewed
• [Journal Article] Defensive reaction against bee venom (2020)
  • Author(s): Kida Misato、Nakamura Tatsuro、Fujiwara Yuki、Murata Takahisa
  • Journal Title: Folia Pharmacologica Japonica Volume: 155 Issue: 4 Pages: 277-277
  • DOI: 10.1254/fpj.20019
  • NAID: 130007867534
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed
• [Journal Article] The profile of lipid metabolites in urine of marmoset wasting syndrome (2020)
  • Author(s): Yamazaki Arisa、Nakamura Tatsuro、Miyabe-Nishiwaki Takako、Hirata Akihiro、Inoue Rikako、Kobayashi Koji、Miyazaki Yusuke、Hamasaki Yuta、Ishigami Akiyo、Nagata Nanae、Kaneko Akihisa、Koizumi Makoto、Ohta Hiroki、Okano Hirotaka James、Murata Takahisa
  • Journal Title: PLOS ONE Volume: 15 Issue: 6 Pages: 1-11
  • DOI: 10.1371/journal.pone.0234634
  • Peer Reviewed / Open Access
• [Journal Article] A novel eicosapentaenoic acid‐derived anti‐inflammatory lipid mediator 5,6‐DiHETE is abundant in blue back fish intestines (2020)
  • Author(s): Kida Misato、Nakamura Tatsuro、Murata Takahisa
  • Journal Title: Journal of Food Science Volume: 85 Issue: 7 Pages: 1983-1987
  • DOI: 10.1111/1750-3841.15179
  • Peer Reviewed
• [Journal Article] The profile of urinary lipid metabolites in cats (2020)
  • Author(s): KOBAYASHI Yui、NAKAMURA Tatsuro、KOBAYASHI Koji、MURATA Takahisa
  • Journal Title: Journal of Veterinary Medical Science Volume: 82 Issue: 7 Pages: 1017-1020
  • DOI: 10.1292/jvms.20-0238
  • NAID: 130007882355
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic potential of D prostanoid receptor 1 signal enhancement in a murine model of food allergy. (2019)
  • Author(s): Nakamura T, Hirai R, Tachibana Y, Masuko S, Nagata N, Murata T.
  • Journal Title: The journal of allergy and clinical and immunology Volume: 印刷中 Issue: 6 Pages: 2290-2293
  • DOI: 10.1016/j.jaci.2019.01.039
  • Peer Reviewed
• [Presentation] 新規炎症抑制脂質5,6-DiHETEの経口投与はマウスのDSS誘導性腸炎を抑制する (2021)
  • Author(s): 竹ノ内晋也、今井大貴、小林幸司、中村達朗、永田奈々恵、村田幸久
  • Organizer: 第94回日本薬理学会年会
• [Presentation] 8-iso PGE2 causes nasal congestion in allergic rhinitis of mice (2021)
  • Author(s): Yuri Tachibana, Tatsuro Nakamura, Takahisa Murata
  • Organizer: 第28回日本血管生物医学会学術集会/28th JVBMO
• [Presentation] 15-hydroxy eicosadienoic acid exacerbates allergic rhinitis by causing vascular hyper-permeability (2021)
  • Author(s): Kana Miyata, Daiki Horikami, Yuri Tachibana, Tatsuro Nakamura, Takahisa Murata
  • Organizer: 第28回日本血管生物医学会学術集会/28th JVBMO
• [Presentation] L-PGDSとH-PGDSは網膜血管新生を促進する (2020)
  • Author(s): 堀上大貴 、堰八英里香 、大森啓介 、小林幸司 、永田奈々恵 、中村達朗 、 倉田薫里 、植村明嘉 、村田幸久
  • Organizer: 第163回日本獣医学会学術集会
• [Presentation] 新規炎症抑制脂質5,6-DiHETEのDSS誘導性腸炎モデルマウスに対する治療効果の検討 (2020)
  • Author(s): 竹ノ内晋也、今井大貴、小林幸司、中村達朗、永田奈々恵、村田幸久
  • Organizer: 第163回日本獣医学会学術集会
• [Presentation] 猫の尿中脂質代謝産物のプロファイル (2020)
  • Author(s): 小林唯 、中村達朗 、米澤智洋 、金学正 、篠崎達也 、小林幸司 、 前田真吾 、村田幸久
  • Organizer: 第163回日本獣医学会学術集会
• [Presentation] 12-HETEはTh2分化を促進させてアレルギー性鼻炎を悪化させる (2020)
  • Author(s): 橘侑里、中村達朗、村田幸久
  • Organizer: 第163回日本獣医学会学術集会
• [Presentation] プロスタグランジンD2を毒仮説から考える (2020)
  • Author(s): 中村達朗、藤原祐樹、木田美聖、村田幸久
  • Organizer: 第2回比較薬理学・毒性学会春季研究会
• [Presentation] 食物アレルギーにおけるPGD2の役割解明と治療、診断への応用 (2020)
  • Author(s): 中村達朗
  • Organizer: 第 93 回 日本薬理学会年会
  • Invited
• [Presentation] Misato Kida, Tatsuro Nakamura, Yuki Fujiwara, Takahisa Murata. (2019)
  • Author(s): The role of PGD2/CRTH2 signaling in host defense against bee venom
  • Organizer: The 68th Annual Meeting of Japanese Society of Allergology
• [Presentation] ハチ毒に対する生体防御反応においてプロスタグランジンD2受容体CRTH2シグナルが果たす役割 (2019)
  • Author(s): 木田美聖、中村達朗、藤原祐樹、村田幸久.
  • Organizer: 第140回日本薬理学会関東部会
• [Presentation] ハチ毒に対する生体防御反応においてプロスタグランジンD2受容体CRTH2シグナルが果たす役割 (2019)
  • Author(s): 木田美聖、中村達朗、藤原祐樹、村田幸久.
  • Organizer: 第162回日本獣医学会学術集会
• [Presentation] The profiling of lipid metabolites in the nasal lavage fluid of a murine model of allergic rhinitis (2019)
  • Author(s): Yuri Tachibana, Tatsuro Nakamura. Takahisa Murata
  • Organizer: World Allergy Congress 2019
  • Int'l Joint Research
• [Presentation] Urinary tetranor-PGDM predicts the change of oral food antigen-induced allergic symptom in mice (2018)
  • Author(s): Tatsuro Nakamura, Rina Hirai, and Takahisa Murata
  • Organizer: 第67回日本アレルギー学会
• [Presentation] Signal enhancement of D prostanoid receptor prevents the development of food allergy (2018)
  • Author(s): Tatsuro Nakamura, Rina Hirai, Takahisa Murata
  • Organizer: 18th World congress of basic and clinical pharmacology
  • Int'l Joint Research
• [Book] Veterinary Immunology for Practitioners (2021)
  • Author(s): 中村達朗、木田美聖、村田幸久
  • Total Pages: 8
  • Publisher: 動物アレルギー検査(株)