The development of anti-allergy therapies targeting several inhibitory receptors

• Project/Area Number: 15K15376
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: Kitaura Jiro 順天堂大学, 医学(系)研究科(研究院), 先任准教授 (30282651)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アレルギー / 抑制型受容体 / 脂質 / マスト細胞

Outline of Final Research Achievements

Binding and reporter assays using an extracellular domain of inhibitory receptors showed that mast cell inhibitory receptors tested, except for LMIR1 and LMIR3, failed to recognize specific lipids. While the binding of ceramide to LMIR3 inhibited FceRI signals in vitro and in vivo, the interaction between phosphatidylserine and LMIR1 failed to do so. Accordingly, the inhibitory effect of vesicles containing both ceramide and phosphatidylserine on FceRI-mediated mast cell activation was weaker than that of vesicles containing ceramide alone. Thus, administering vesicles containing lipid ligands for LMIR3 might be effective for allergic diseases.

Research Products

• [Journal Article] Ceramide-CD300f Binding Inhibits Lipopolysaccharide-induced Skin Inflammation. (2017)
  • Author(s): Shiba E, Izawa K, Kaitani A, Isobe M, Maehara A, Uchida K, Maeda K, Nakano N, Ogawa H, Okumura K, Kitamura T, Shimizu T, Kitaura J
  • Journal Title: J Biol Chem. Volume: 292 Issue: 7 Pages: 2924-2932
  • DOI: 10.1074/jbc.m116.768366
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation. (2015)
  • Author(s): Matsukawa T, Izawa K, Isobe M, Takahashi M, Maehara A, Yamanishi Y, Kaitani A, Okumura K, Teshima T, Kitamura T, Kitaura J
  • Journal Title: Gut Volume: 印刷中 Issue: 5 Pages: 1-11
  • DOI: 10.1136/gutjnl-2014-308900
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The phosphatidylserine and phosphatidylethanolamine receptor CD300a binds dengue virus and enhances infection. (2015)
  • Author(s): Carnec X, Meertens L, Dejarnac O, Perera-Lecoin M, Lamine Hafirassou M, Kitaura J, Ramdasi R, Schwartz O, Amara A
  • Journal Title: J Virol Volume: 90 Issue: 1 Pages: 92-102
  • DOI: 10.1128/jvi.01849-15
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Transcription Factor Ehf Is Involved in TGF-β-Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells. (2015)
  • Author(s): Yamazaki S, Nakano N, Honjo A, Hara M, Maeda K, Nishiyama C, Kitaura J, Ohtsuka Y, Okumura K, Ogawa H, Shimizu T
  • Journal Title: Journal of immunology Volume: 195(7) Issue: 7 Pages: 3427-3435
  • DOI: 10.4049/jimmunol.1402856
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Ceramide-CD300f interaction inhibits Mrgprb2-mediated pseudo-allergic drug reactions in mice. (2017)
  • Author(s): Hatayama Tomoki, Takamori Ayako, Izawa Kumi, Maehara Akie, Isobe Masamichi, Kaitani Ayako, Uchida Shino, Nakano Nobuhiro, Maeda Keiko, Ando Tomoaki, Okumura Ko, Kitamura Toshio, Kitaura Jiro
  • Organizer: 第45回日本免疫学会
  • Place of Presentation: Okinawa Convention Center・Laguna Garden Hotel、沖縄
  • Year and Date: 2017-12-07
• [Presentation] 敗血症性腹膜炎におけるセラミド-CD300fシグナルの役割 (2016)
  • Author(s): 伊沢久未、奥村康、北浦次郎
  • Organizer: 第９回セラミド研究会学術集会
  • Place of Presentation: 東京ユビキタス協創広場CANVAS、東京
  • Year and Date: 2016-10-27
• [Presentation] Inhibition of allergic responses by ceramide-CD300f axis. (2016)
  • Author(s): Jiro Kitaura
  • Organizer: Federation of American Societies for Experimental Biology (FASEB): IgE and Allergy: 50 Years and Onward
  • Place of Presentation: West Palm Beach, Florida (USA)
  • Year and Date: 2016-07-25
  • Int'l Joint Research / Invited
• [Presentation] Disrupting ceramide-LMIR3 interaction prevents bacterial sepsis by stimulating neutrophil recruitment (2015)
  • Author(s): 伊沢久未、磯部優理、奥村康、北村俊雄、北浦次郎
  • Organizer: 第43回日本臨床免疫学会
  • Place of Presentation: 神戸国際会議場兵庫県）
  • Year and Date: 2015-10-22
• [Presentation] セラミドによるアレルギー性炎症の制御 (2015)
  • Author(s): 北浦次郎
  • Organizer: 第64 回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
  • Year and Date: 2015-05-28
  • Invited
• [Presentation] マウスおよびヒトLMIR3のリガンド同定と機能解析 (2015)
  • Author(s): 伊沢久未、奥村康、北村俊雄、北浦次郎
  • Organizer: 第64回日本アレルギー学会学術大会
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
  • Year and Date: 2015-05-26