Analysis of the mechanisms by which mast cell activation is regulated by paired receptors LMIR3 and LMIR7

• Project/Area Number: 26293231
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• 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), 准教授 (30282651)
• Co-Investigator(Kenkyū-buntansha): 北村 俊雄 東京大学, 医科学研究所, 教授 (20282527)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: アレルギー / 炎症 / マスト細胞 / 抑制型受容体 / 活性化型受容体 / ペア型受容体 / アレルギー・ぜんそく / アレルギー・炎症

Outline of Final Research Achievements

LMIR3-deficient colonic mast cells were pivotal in the exacerbation of DSS-induced colitis in LMIR3-deficeint mice. Ceramide vesicles attenuated DSS-induced colitis by inhibiting ATP-mediated activation of colonic mast cells through ceraimide-LMIR3 binding. On the other hand, LMIR3-deficient mice were highly resistant to septic peritonitis induced by cecal ligation and puncture (CLP). Ceramide-LMIR3 binding inhibited the release of neutrophil chemoattractaaants from mast cells and neutrophils in response to E. coli, thereby suppressing neutrophil recruitment to sites of infection. Accordingly, disrupting ceramide-LMIR3 interactions prevents septic peritonitis by stimulating neutrophil recruitment.

Research Products

• [Int'l Joint Research] University Hospital Erlangen/Technische Universität Dresden(Germany)
• [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] Pharmacological inhibition of Notch signaling suppresses food antigen-induced mucosal mast cell hyperplasia. (2017)
  • Author(s): Honjo A, Nakano N, Yamazaki S, Hara M, Uchida K, Kitaura J, Nishiyama C, Yagita H, Ohtsuka Y, Ogawa H, Okumura K, Shimizu T
  • Journal Title: J Allergy Clin Immunol. Volume: 139 Issue: 3 Pages: 987-996
  • DOI: 10.1016/j.jaci.2016.05.046
  • 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
• [Journal Article] A C-terminal mutant of CCAAT-enhancer-binding protein α (C/EBPα-C(m)) downregulates Csf1r, a potent accelerator in the progression of acute myeloid leukemia with C/EBPα-C(m). (2015)
  • Author(s): Togami K, Kitaura J, Uchida T, Inoue D, Nishimura K, Kawabata KC, Nagase R, Horikawa S, Izawa K, Fukuyama T, Nakahara F, Oki T, Harada Y, Harada H, Aburatani H, Kitamura T.
  • Journal Title: Exp Hematol. Volume: 43(4) Issue: 4 Pages: 300-308
  • DOI: 10.1016/j.exphem.2014.11.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS. (2015)
  • Author(s): Inoue D, Kitaura J, Matsui H, Hou HA, Chou WC, Nagamachi A, Kawabata KC, Togami K, Nagase R, Horikawa S, Saika M, Micol JB, Hayashi Y, Harada Y, Harada H, Inaba T, Tien HF, Abdel-Wahab O, Kitamura T.
  • Journal Title: Leukemia Volume: 29(4) Issue: 4 Pages: 847-57
  • DOI: 10.1038/leu.2014.301
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hes1 promotes blast crisis in chronic myelogenous leukemia through MMP-9 upregulation in leukemic cells. (2014)
  • Author(s): Nakahara F, Kitaura J, Uchida T, Nishida C, Togami K, Inoue D, Matsukawa T, Kagiyama Y, Enomoto Y, Kawabata KC, Chen-Yi L, Komeno Y, Izawa K, Oki T, Nagae G, Harada Y, Harada H, Otsu M, Aburatani H, Heissig B, Hattori K, Kitamura T.
  • Journal Title: Blood Volume: 123(25) Issue: 25 Pages: 3932-42
  • DOI: 10.1182/blood-2013-01-476747
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Leukocyte mono-immunoglobulin-like receptor 6 (LMIR6) is an activating receptor expressed in patrolling monocytes. (2016)
  • Author(s): Isobe Masamichi, Takamori Ayako, Izawa Kumi, Maehara Akie, 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: 2016-12-07
• [Presentation] Ceramide-CD300f interaction inhibits Mrgprb2-mediated pseudo-allergic drug reactions in mice. (2016)
  • 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: 2016-12-07
• [Presentation] A critical role of ceramide-CD300f interaction in septic peritonitis. (2016)
  • Author(s): Izawa Kumi, Maehara Akie, Isobe Masamichi, Kaitani Ayako, Nakano Nobuhiro, Maeda Keiko, Takamori Ayako, 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: 2016-12-06
• [Presentation] CD300f suppresses LPS-induced skin inflammation. (2016)
  • Author(s): Watanabe Daiki, Izawa Kumi, Kaitani Ayako, Maehara Akie, Isobe Masamichi, Takamori 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: 2016-12-06
• [Presentation] The role of leukocyte mono-immunoglobulin-like receptor 8 (LMIR8)/CLM-6 in plasmacytoid dendritic cell (pDC) (2016)
  • Author(s): Kaitani Ayako, Izawa Kumi, Maehara Akie, Isobe Masamichi, Takamori 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: 2016-12-05
• [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] マスト細胞に発現する活性化型受容体LMIR7のアレルギー反応にける役割 (2016)
  • Author(s): 伊沢久未、奥村康、北村俊雄、北浦次郎
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京国際フォーラム、東京
  • Year and Date: 2016-06-17
• [Presentation] The regulatory role of a novel activating receptor in mast cell- and IgE-dependent anaphylaxis (2016)
  • Author(s): Jiro Kitaura
  • Organizer: 31st Symposium of the Collegium Internationale Allergologicum
  • Place of Presentation: Charleston, South Carolina（USA）
  • Year and Date: 2016-04-07
  • Int'l Joint Research
• [Presentation] The novel role of LMIR7/CLM-3 in mast cell- and IgE-dependent anaphylaxis (2015)
  • Author(s): Isobe Masamichi, Izawa Kumi, Maehara Akie, Matsukawa Toshihiro, Kaitani Akie, Okumura Ko, Kitamura Toshio, Kitaura Jiro
  • Organizer: 第44回日本免疫学会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2015-11-18
• [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
• [Presentation] Ceramide-CD300f binding suppresses experimental colitis by inhibiting ATP-mediated mast cell activation. (2015)
  • Author(s): Matsukawa Toshihiro, Izawa Kumi, Okumura Ko, Teshima Takanori, Kitamura Toshio, Kitaura Jiro
  • Organizer: THE AMERICAN ASSOCIATION OF IMMUNOLOGISTS IMMUNOLOGY 2015
  • Place of Presentation: NEW ORLEANS (AMERICA)
  • Year and Date: 2015-05-10
  • Int'l Joint Research
• [Presentation] ペア型受容体LMIR/CD300による敗血症の制御機構 (2015)
  • Author(s): 北浦次郎
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18
  • Invited
• [Presentation] 抑制型受容体LMIR3/CD300fによるアレルギー・炎症性疾患の制御メカニズム (2015)
  • Author(s): 北浦次郎
  • Organizer: 第143回御茶ノ水木曜会
  • Place of Presentation: 順天堂大学
  • Year and Date: 2015-03-12
  • Invited
• [Presentation] セラミドを認識する抑制型受容体LMIR3/CD300fによるアレルギー・炎症の制御機構 (2015)
  • Author(s): 北浦次郎
  • Organizer: 第10回順天堂眼アレルギー研究会
  • Place of Presentation: ホテル東京ガーデンパレス
  • Year and Date: 2015-03-04
  • Invited
• [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
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-12-12
• [Presentation] LMIR3/CD300f deficiency aggravates DSS-induced colitis (2014)
  • Author(s): Matsukawa Toshihiro, Izawa Kumi, Isobe Masamichi, Takahashi Mariko, Maehara Akie, Kaitani Ayako, Okumura Ko, Kitamura Toshio, Kitaura Jiro
  • Organizer: 第43回日本免疫学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-12-11
• [Presentation] 抑制型レセプターLMIR3/CD300fの欠損はDSS腸炎を悪化させる (2014)
  • Author(s): 松川敏大、伊沢久未、北村俊雄、北浦次郎
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-26
• [Presentation] ペア型受容体LMIR/CD300ファミリーとアレルギー・炎症 (2014)
  • Author(s): 北浦次郎
  • Organizer: 御茶ノ水がん学アカデミア第106回集会
  • Place of Presentation: 順天堂大学
  • Year and Date: 2014-10-22
  • Invited
• [Remarks] 炎症性腸疾患の発症・進展を抑制する仕組みを解明
  • URL: https://www.juntendo.ac.jp/graduate/pdf/news16.pdf
• [Remarks] 炎症性腸疾患の発症・進展を抑制する仕組みを解明
  • URL: http://www.juntendo.ac.jp/graduate/pdf/news16.pdf