What is a ligand for CD200R3 that elicits inflammation?

• Project/Area Number: 15K20969
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Collagenous pathology/Allergology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: YAMANISHI Yoshinori 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (10735244)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アレルギー / 炎症 / ペア型レセプター / 好塩基球 / マスト細胞 / 免疫レセプター

Outline of Final Research Achievements

CD200R3 is a DAP12-coupled activating receptor selectively expressed by basophils and mast cells. Crosslinking of CD200R3 with an anti-CD200R3 agonistic antibody (anti-CD200R3 Ab) reportedly induces degranulation and cytokine production of basophils and mast cells, leading to systemic and local anaphylactoid reactions in mice. In this study, we sought to determine pathophysiological roles of CD200R3 in the development of inflammation through identification of a novel CD200R3 ligand(s) and analysis of CD200R3-deficient mice. Although a CD200R3 ligand has not yet been identified as far as we tested, CD200R3-deficient basophils and mast cells failed to degranulate and produce cytokines when stimulated with anti-CD200R3 Ab in vitro. Moreover, CD200R3-deficient mice showed a lack of anti-CD200R3 Ab-elicited systemic and local anaphylactoid reactions. Thus, CD200R3 appears to be an activating receptor that contributes to the development of a certain type of allergic inflammation.

Research Products

• [Journal Article] The CD300e molecule in mice is an immune-activating receptor. (2018)
  • Author(s): Isobe M, Izawa K, Sugiuchi M, Sakanishi T, Kaitani A, Takamori A, Maehara A, Matsukawa T, Takahashi M, Yamanishi Y, Oki T, Uchida S, Uchida K, Ando T, Maeda K, Nakano N, Yagita H, Takai T, Ogawa H, Okumura K, Kitamura T, Kitaura J.
  • Journal Title: J Biol Chem. Volume: 293 Issue: 10 Pages: 3793-3805
  • DOI: 10.1074/jbc.ra117.000696
  • Peer Reviewed / Open Access
• [Journal Article] Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment. (2017)
  • Author(s): Izawa K, Maehara A, Isobe M, Yasuda Y, Urai M, Hoshino Y, Ueno K, Matsukawa T, Takahashi M, Kaitani A, Shiba E, Takamori A, Uchida S, Uchida K, Maeda K, Nakano N, Yamanishi Y, Oki T, Voehringer D, Roers A, Nakae S, Ishikawa J, Kinjo Y, Shimizu T, Ogawa H, Okumura K, Kitamura T, Kitaura J
  • Journal Title: Sci Rep. Volume: 7(1) Issue: 1 Pages: 4298-4298
  • DOI: 10.1038/s41598-017-04647-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Recent advances in understanding basophil-mediated Th2 immune responses (2017)
  • Author(s): Yamanishi Yoshinori、Miyake Kensuke、Iki Misako、Tsutsui Hidemitsu、Karasuyama Hajime
  • Journal Title: Immunological Reviews Volume: 278 Issue: 1 Pages: 237-245
  • DOI: 10.1111/imr.12548
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Differential usage of COX-1 and COX-2 in prostaglandin production by mast cells and basophils (2017)
  • Author(s): Bando, T., Fujita, S., Nagano, N., Hayashi, A., Yoshikawa, S., Yamanishi, Y., Minami, M., Tada, H., Kishikawa, K., and Karasuyama, H.
  • Journal Title: Biochem Biophys Rep. Volume: 10 Pages: 82-87
  • DOI: 10.1016/j.bbrep.2017.03.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Skin CD4+ Memory T Cells Play an Essential Role in Acquired Anti-Tick Immunity through Interleukin-3-Mediated Basophil Recruitment to Tick-Feeding Sites (2017)
  • Author(s): Ohta Takuya、Yoshikawa Soichiro、Tabakawa Yuya、Yamaji Kayoko、Ishiwata Kenji、Shitara Hiroshi、Taya Choji、Oh-hora Masatsugu、Kawano Yohei、Miyake Kensuke、Yamanishi Yoshinori、Yonekawa Hiromichi、Watanabe Naohiro、Kanuka Hirotaka、Karasuyama Hajime
  • Journal Title: Frontiers in Immunology Volume: 8 Pages: 1348-1348
  • DOI: 10.3389/fimmu.2017.01348
  • Peer Reviewed / Open Access
• [Journal Article] Multifaceted roles of basophils in health and disease (2017)
  • Author(s): Karasuyama H, Miyake K, Yoshikawa S, Yamanishi Y
  • Journal Title: J Allergy Clin Immunol Volume: S0091-6749 Issue: 2 Pages: 31894-31898
  • DOI: 10.1016/j.jaci.2017.10.042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 皮膚バリアにおける好塩基球の重要性 (2017)
  • Author(s): 長尾俊久, 山西吉典, 烏山 一
  • Journal Title: 実験医学 Volume: 35 Pages: 1123-1128
• [Journal Article] 好塩基球トリプターゼmMCP-11 はIgE 依存的慢性アレルギー炎症の誘 導に重要な役割を果たす (2017)
  • Author(s): 壹岐美紗子, 山西吉典, 烏山 一
  • Journal Title: 臨床免疫・アレルギー科 Volume: 68 Pages: 19-24
• [Journal Article] 好塩基球による免疫応答制御 (2017)
  • Author(s): 長尾峻久, 山西吉典, 烏山一
  • Journal Title: 血液内科 Volume: 75 Pages: 130-136
• [Journal Article] MIP-1α/CCL3-expressing basophil-lineage cells drive the leukemic hematopoiesis of chronic myeloid leukemia in mice. (2016)
  • Author(s): Baba T, Tanabe Y, Yoshikawa S, Yamanishi Y, Morishita S, Komatsu N, Karasuyama H, Hirao A, Mukaida N
  • Journal Title: Blood Volume: 印刷中 Issue: 21 Pages: 2607-17
  • DOI: 10.1182/blood-2015-10-673087
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Basophils and mast cells in immunity and inflammation. (2016)
  • Author(s): Yamanishi, Y., and Karasuyama, H.
  • Journal Title: Semin. Immunopathol. Volume: 38 Issue: 5 Pages: 535-537
  • DOI: 10.1007/s00281-016-0582-0
  • Peer Reviewed / Open Access
• [Journal Article] Basophil-derived IL-4 plays versatile roles in immunity (2016)
  • Author(s): Yamanishi, Y., and Karasuyama, H.
  • Journal Title: Semin. Immunopathol. Volume: 38 Issue: 5 Pages: 615-622
  • DOI: 10.1007/s00281-016-0568-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Real-time imaging of mast cell degranulation in vitro and in vivo (2016)
  • Author(s): Horiguchi, K., Yoshikawa, S., Saito, A., Haddad, S., Ohta, T., Miyake, K., Yamanishi, Y., and Karasuyama, H.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 479 Issue: 3 Pages: 517-522
  • DOI: 10.1016/j.bbrc.2016.09.100
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation in mice (2016)
  • Author(s): Iki, M., Tanaka, K., Deki, H., Fujimaki, M., Sato, S., Yoshikawa, S., Yamanishi, Y., and Karasuyama, H.
  • Journal Title: Blood Volume: 128 Issue: 25 Pages: 2909-2918
  • DOI: 10.1182/blood-2016-07-729392
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Novel CD200 homologues iSEC1 and iSEC2 are gastrointestinal secretory cell-specific ligands of inhibitory receptor CD200R (2016)
  • Author(s): Kojima, T., Tsuchiya, K., Ikemizu, S., Yoshikawa, S., Yamanishi, Y., Watanabe, M., and Karasuyama, H.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 36457-36457
  • DOI: 10.1038/srep36457
  • 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] TREM2 sustains microglial expansion during aging and response to demyelination. (2015)
  • Author(s): Poliani PL, Wang Y, Fontana E, Robinette ML, Yamanishi Y, Gilfillan S, Colonna M.
  • Journal Title: J Clin Invest. Volume: 125 Issue: 5 Pages: 2161-2170
  • DOI: 10.1172/jci77983
  • Peer Reviewed / Open Access
• [Journal Article] Large particulate allergens can elicit mast cell-mediated anaphylaxis without exit from blood vessels as efficiently as do small soluble allergens (2015)
  • Author(s): LiHua Li, Takuya Ohta, Kayo Horiguchi, Yohei Kawano, Hiroshi Ohtsu, Yoshinori Yamanishi, MD., Hajime Karasuyama.
  • Journal Title: Biochem Biophys Res Commun Volume: 467 Issue: 1 Pages: 70-75
  • DOI: 10.1016/j.bbrc.2015.09.120
  • Peer Reviewed
• [Presentation] Basophil tryptase mMCP-11 plays a crucial role in the IgE-mediated chronic allergic inflammation (2017)
  • Author(s): Yoshinori Yamanishi, Misako Iki, Kensei Tanaka, Hayato Deki, Mio Fujimaki, Shingo Sato, Soichiro Yoshikawa, Hajime Karasuyama
  • Organizer: The 66th Annual Meeting of Japanese Society of Allergology
• [Presentation] COPD の病態における炎症性単球、間質 マクロファージの役割 (2017)
  • Author(s): 柴田翔, 立石知也, 吉川宗一郎, 山西吉典, 稲瀬直彦, 烏山一
  • Organizer: The 66th Annual Meeting of Japanese Society of Allergology
• [Presentation] 好塩基球による皮膚アレルギー炎症の調節 (2017)
  • Author(s): 山西吉典
  • Organizer: 第３５回呼吸器・ 免疫シンポジウム
  • Invited
• [Presentation] Prolonged Ca2+ influx via STIM2 is essential for cytokine-induced IL-4 production in basophil (2017)
  • Author(s): Soichiro Yoshikawa, Masatsugu Oh-hora, Kensuke Miyake, Yohei Kawano, Yoshinori Yamanishi, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Monocyte-derived macrophages in the lung contribute to the development of pulmonary emphysema through MMP12 production in a mouse model of COPD (2017)
  • Author(s): Sho Shibata, Kensuke Miyake, Soichiro Yoshikawa, Yohei Kawano, Yoshinori Yamanishi, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Basophil tryptase mMCP-11 plays a crucial role in IgE-mediated, delayed-onset allergic inflammation (2017)
  • Author(s): Yoshinori Yamanishi, Misako Iki, Kensei Tanaka, Hayato Deki, Mio Fujimaki, Kensuke Miyake, Soichiro Yoshikawa, Yohei Kawano, Shingo Sato, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Basophils exert antigen presentation via trogocytosis-mediated acquisition of peptide-MHC clas II complexes from dendritic cells (DCs) (2017)
  • Author(s): Kensuke Miyake, Nozomu Shiozawa, Toshihisa Nagao, Soichiro Yoshikawa, Yoshinori Yamanishi, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] The basophil-specific protease mMCP-8 provokes an inflammatory response in the skin with microvascular hyperpermeability and leukocyte infiltration (2017)
  • Author(s): Hidemitsu Tsutsui, Yoshinori Yamanishi, Hiromi Ohtsuka, Shingo Sato, Soichiro Yoshikawa, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Histamine plays a critical role in acquired protective immunity against tick infestation (2017)
  • Author(s): Yuya Tabakawa, Takuya Ohta, Soichiro Yoshikawa, Kayoko Yamaji, Kenji Ishiwata, Yohei Kawano, Yoshinori Yamanishi, Naohiro Watanabe, Hiroshi Ohtsu, Hirotaka Kanuka, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Sugar modification of carrier protein confers ability on allergen to induce IgEand basophil-mediated allergic inflammation (2017)
  • Author(s): Toshihisa Nagao, Mio Teranishi, Kensuke Miyake, Soichiro Yoshikawa, Yohei Kawano, Yoshinori Yamanishi, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Differential usage of COX-1 and COX-2 in prostaglandin production by mast cells and basophils (2017)
  • Author(s): Tomoyuki Bando, Setsuko Fujita, Naoko Nagano, Soichiro Yoshikawa, Yoshinori Yamanishi, Masashi Minami, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] Novel CD200 hologues iSEC1 and I SEC2 are gastrointestinal secretory cell-specific ligands of inhibitory receptor CD200R (2017)
  • Author(s): Toshiyuki Kojima, Soichiro Yoshikawa, Yoshinori Yamanishi, Hajime Karasuyama
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology
• [Presentation] STIM2 plays essential role in cytokine- induced IL-4 production in basophils (2016)
  • Author(s): Yoshikawa, S., Oh-hora, M., Yamanishi, Y., Karasuyama, H
  • Organizer: The 45th Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: 沖縄コンベンションセンター、沖縄県
  • Year and Date: 2016-12-05
• [Presentation] Basophil-selective mMCP-11 plays crucial roles in the development of IgE-mediated chronic allergic inflammation in the skin (2016)
  • Author(s): Iki, M., Tanaka, K., Deki, H., Nagao, T, Horibe, M., Sato, S., Yoshikawa, S., Yamanishi Y., Karasuyama, H
  • Organizer: The 45th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 沖縄コンベンションセンター、沖縄県
  • Year and Date: 2016-12-05
• [Presentation] Basophils gain the capacity of antigen presentation by acquiring MHC class II molecules from dendritic cells through trogocytosis (2016)
  • Author(s): Miyake, K., Shiozawa, N., Nagao, T., Kawawa, M., Yoshikawa, S., Yamanishi, Y., Karasuyama, H
  • Organizer: The 45th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 沖縄コンベンションセンター、沖縄県
  • Year and Date: 2016-12-05
• [Presentation] STIM1/2 plays essential role in basophil activation and development of IgE-mediated chronic allergic inflammation. (2016)
  • Author(s): Yoshikawa, S., Oh-hora, M., Adachi, T., Yamanishi, Y., karasuyama, H.
  • Organizer: International Congress of Immunology
  • Place of Presentation: Melbourne Convention and Exhibition Centre,オーストラリア
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Sugar modification of carrier protein in allergen determines the magnitude of IgE- and basophil-mediated allergic inflammation (2016)
  • Author(s): Nagao, T., Takahashi, S., Kawawa, M., Miyake, K., Yoshikawa, S., Yamanishi, Y., Karasuyama, H
  • Organizer: International Congress of Immunology
  • Place of Presentation: Melbourne Convention and Exhibition Centre, オーストラリア
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] mMCP-8, a basophil specific pro- tease, triggers an inflammatory response by stimulating fibroblasts to produce chemokines (2016)
  • Author(s): Tsutsui, H., Yamanishi, Y., Yoshikawa, S., Sato, S., Karasuyama, H
  • Organizer: International Congress of Immunology
  • Place of Presentation: Melbourne Convention and Exhibition Centre, オーストラリア
  • Year and Date: 2016-08-21
  • Int'l Joint Research
• [Presentation] Basophil-specific protease mMCP-8 triggers skin inflammation through activation of dermal fibroblasts. (2015)
  • Author(s): TSUTSUI Hidemitsu, YAMANISHI Yoshinori, TATEBAYASHI Satoru, YOSHIKAWA Soichiro, SATO Shingo, KARASUYAMA Hajime
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Year and Date: 2015-11-18
• [Presentation] Basophils acquire MHC class II molecules from DCs and exert antigen presenting capacity. (2015)
  • Author(s): MIYAKE Kensuke, SHIOZAWA Nozomu, NAGAO Toshihisa, YAHAGI Yuto, YOSHIKAWA Soichiro, YAMANISHI Yoshinori, KARASUYAMA Hajime
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Year and Date: 2015-11-18
• [Presentation] Molecular properties of carrier protein in allergen are critical for the development of IgE-mediated chronic allergic inflammation in the skin: what makes a foreign material to be an allergen? (2015)
  • Author(s): NAGAO Toshihisa, TAKAHASHI Saori, KAWAWA Moe, MIYAKE Kensuke, YOSHIKAWA Soichiro, SATO Shingo, YAMANISHI Yoshinori, KARASUYAMA Hajime
  • Organizer: 第４４回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌市）
  • Year and Date: 2015-11-18
• [Book] 臨床検査 (2016)
  • Author(s): 山西吉典
  • Total Pages: 7
  • Publisher: 医学書院
• [Book] クリニックマガジン (2016)
  • Author(s): 山西吉典
  • Total Pages: 1
  • Publisher: クリニックマガジン社
• [Book] アレルギー・免疫 (2016)
  • Author(s): 山西吉典、烏山一
  • Total Pages: 7
  • Publisher: 医薬ジャーナル社
• [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 免疫アレルギー学分野
  • URL: https://immune-regulation.org/
• [Remarks] 東京医科歯科大学 大学院医歯学総合研究科 免疫アレルギー学分野
  • URL: http://immune-regulation.org/