Functional analysis of human LMIR3/CD300F

• Project/Area Number: 25893050
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Collagenous pathology/Allergology
• Research Institution: The University of Tokyo
• Principal Investigator: IZAWA Kumi 東京大学, 医科学研究所, 助教 (80708313)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マスト細胞 / アレルギー / IgE / スフィンゴミエリン / セラミド / 免疫学

Outline of Final Research Achievements

Leukocyte mono-immunoglobulin-like receptor (LMIR) belongs to a paired activating and inhibitory receptor family. Mouse LMIR3 (mLMIR3)/CD300f
is an inhibitory receptor containing 2 immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and a single immunoreceptor tyrosine-based switch motif (ITSM).We have recently demonstrated that extracellular ceramide is a ligand for mLMIR3/CD300f, which is a negative regulator of high-affinity IgE receptor (FcεRI)-mediated activation of mast cells. Although ceramide is a major ligand for mLMIR3, both sphingomyelin and ceramide act as physiological ligands for hLMIR3 in mast cells, thereby inhibiting FcεRI-mediated activation of mast cells. These results will help understand the intrinsic mechanism by which excessive activation of mast cells is prevented in human beings, leading to the development of novel therapeutic strategies against allergic diseases.

Research Products

• [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] Sphingomyelin and ceramide are physiological ligands for human LMIR3/CD300f, inhibiting FceRI-mediated mast cell activation. (2014)
  • Author(s): Izawa, K., Isobe, M., Matsukawa, T., Ito, S., Maehara, A., Takahashi, M., Yamanishi, Y., Kaitani, A., Oki, T., Okumura, K., *Kitamura, T., and *Kitaura, J.
  • Journal Title: J. Allergy. Clin. Immunol. Volume: 133 Issue: 1 Pages: 270-273
  • DOI: 10.1016/j.jaci.2013.08.008
  • Peer Reviewed
• [Presentation] Disrupting ceramide-LMIR3 interaction prevents bacterial sepsis by stimulating neutrophil recruitment (2014)
  • Author(s): IZAWA Kumi, ISOBE Masamichi, MATSUKAWA Toshihiro, MAEHARA Akie, TAKAHASHI Mariko, KAITANI Ayako, OKUMURA Ko, KITAMURA Toshio, KITAURA Jiro
  • Organizer: 第43回日本免疫学会・学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-12
• [Presentation] Sphingomyelin and ceramide are physiological ligands for human LMIR3/CD300f, inhibiting FcεRI-mediated mast cell activation. (2013)
  • Author(s): Izawa Kumi, Isobe Masamichi, Matsukawa Toshihiro, Maehara Akie, Yamanishi Yoshinori, Takahashi Mariko, Kaitani Ayako, Okumura Ko, Kitamura Toshio, Kitaura Jiro
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ
• [Presentation] Soluble form of TIM-4 regulates mast cell activation by binding to LMIR5 and TIM-3. (2013)
  • Author(s): Kamachi Fumitaka, Harada Norihiro, Nishiyama Chiharu, Izawa Kumi, Kitaura Jiro, Okumura Ko, Miyake Sachiko, Akiba Hisaya
  • Organizer: 日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ
• [Book] 炎症と免疫 (2014)
  • Author(s): 北浦次郎、伊沢久未、北村俊雄
  • Total Pages: 4
  • Publisher: 先端医学社
• [Book] 生化学 (2013)
  • Author(s): 北浦次郎、伊沢久未、北村俊雄
  • Total Pages: 5
  • Publisher: 日本生化学会
• [Book] 臨床免疫・アレルギー科 (2013)
  • Author(s): 北浦次郎、伊沢久未、山西吉典、北村俊雄
  • Total Pages: 6
  • Publisher: 科学評論社
• [Book] 臨床免疫・アレルギー科 (2013)
  • Author(s): 北浦次郎、伊沢久未、北村俊雄
  • Total Pages: 8
  • Publisher: 科学評論社