Development of a new therapy against allergic asthma

• Project/Area Number: 24390205
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Tsukuba
• Principal Investigator: TAHARA Satoko 筑波大学, 医学医療系, 講師 (20360589)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 喘息 / アラジン－１ / 肥満細胞 / 樹状細胞 / 高親和性IgE受容体 / ITIM / 重症喘息 / アレルギー / 抗体療法 / アラジン-1

Outline of Final Research Achievements

Allergin-1 is an immunotyrosine-based inhibitory motif (ITIM)-bearing immunoglobulin-like receptor and inhibit FcεRI-mediated activating signal in mast cell (MC). We found that Allergin-1 suppress house dust mite (HDM)-induced serum IgE elevation, lung eosinophilia, and methacholin-induced airway hyperresponsiveness (AHR) in vivo. We also found that treatment of mice with Allergin-1-ligand inhibited IgE-dependent passive cutaneous anaphylaxis in vivo. These results indicate that Allergin-1 may be a promising target molecule for therapy against allergic asthma.

Research Products

• [Journal Article] CD155 (PVR/Necl5) mediates a costimulatory signal in CD4+ T cells and regulates allergic inflammations (2015)
  • Author(s): Yamashita Y, Takahashi Y, Wang Y, Tahara-Hanaoka S, Honda S, Bernhardt G, Shibuya A, Shibuya K.
  • Journal Title: J Immunol Volume: -
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Influence of MILR1 promoter polymorphism on expression levels and the phenotype of atopy. (2014)
  • Author(s): Nanatsue K, Ninomiya T, Tsuchiya M, Tahara-Hanaoka S, Shibuya A, Masuko H, Sakamoto T, Hizawa N, Arinami T, Noguchi E.
  • Journal Title: J Hum Genet Volume: 59(9) Issue: 9 Pages: 480-483
  • DOI: 10.1038/jhg.2014.57
  • Peer Reviewed
• [Journal Article] Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated infammatory monocyte migration (2014)
  • Author(s): Naoya T otsuka, Yun-Gi Kim, Kazumasa Kanemaru, Kouta Niizuma, Eiji Umemoto, Kei Nagai, Satoko T ahara-Hanaoka, Chigusa Nakahasi-Oda, Shin-ichiro Honda, Masayuki Miyasaka, Kazuko Shibuya & Akira Shibuya
  • Journal Title: Nature Communications Volume: 5:4710 Issue: 1 Pages: 4710-4710
  • DOI: 10.1038/ncomms5710
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PPARβ/δ activation of CD300a controls intestinal immunity. (2014)
  • Author(s): Tanaka T, Tahara-Hanaoka S, Nabekura T, Ikeda K, Jiang S, Tsutsumi S, Inagaki T, Magoori K, Higurashi T, Takahashi H, Tachibana K, Tsurutani Y, Raza S, Anai M, Minami T, Wada Y, Yokote K, Doi T, Hamakubo T, Auwerx J, Gonzalez FJ, Nakajima A, Aburatani H, Naito M, Shibuya A, Kodama T, Sakai J.
  • Journal Title: Sci Rep Volume: 4 Issue: 1 Pages: 5412-5412
  • DOI: 10.1038/srep05412
  • Peer Reviewed / Open Access
• [Journal Article] Expression and function of Allergin-1 on human primary mast cells (2013)
  • Author(s): Nagai K, Tahara-Hanaoka S, Morishima Y, et al
  • Journal Title: PLoS One Volume: 8(10) Issue: 10 Pages: 1-8
  • DOI: 10.1371/journal.pone.0076160
  • Peer Reviewed
• [Journal Article] Establishment and Characterization of a Novel Anti-DNAM-1 Monoclonal Antibody (2013)
  • Author(s): Yamashita Y, Abe F, Hirochika R, Tahara-Hanaoka S, Shibuya A, Shibuya K.
  • Journal Title: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Volume: 32(1) Issue: 1 Pages: 60-64
  • DOI: 10.1089/mab.2012.0083
  • Peer Reviewed
• [Journal Article] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor. (2012)
  • Author(s): Nakahashi-Oda, C., Tahara-Hanaoka, S., Shoji, M., Okoshi, Y., Nakano-Yokomizo, T., Ohkohchi, N., Yasui, T., Kikutani, H., Honda, S., Shibuya, K., Nagata, S. and Shibuya, A.
  • Journal Title: J Exp. Med. Volume: 209 Issue: 8 Pages: 1493-1503
  • DOI: 10.1084/jem.20120096
  • Peer Reviewed
• [Journal Article] Identification of phosphatidylserine as a ligand for the CD300a immunoreceptor (2012)
  • Author(s): Chigusa Nakahashi-Oda, et.al.
  • Journal Title: BBRC Volume: 417 Issue: 1 Pages: 646-650
  • DOI: 10.1016/j.bbrc.2011.12.025
  • Peer Reviewed
• [Presentation] Allergin-1 on mast cells selectively suppresses airway hyperresponsiveness in house dust mite-induced allergic airway inflammation in mice (2014)
  • Author(s): Hitomi K, Tahara-Hanaoka S, Kubo M, Shibuya A
  • Organizer: 第43 回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-11
• [Presentation] Identification and characterization of human CD300H, the eighth member of the CD300-family receptors (2014)
  • Author(s): Niizuma K, Tahara-Hanaoka S, Noguchi E, Shibuya A
  • Organizer: 第43 回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-11
• [Presentation] Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration (2014)
  • Author(s): Totsuka N, Kim YG, Kanemaru K, Niizuma K, Umemoto E, Nagai K, Tahara-Hanaoka S, Nakahashi-Oda C, Honda S, Miyasaka M, Shibuya K, Shibuya A
  • Organizer: 第43 回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-11
• [Presentation] 暴走する免疫～アレルギーと自己免疫病～ (2014)
  • Author(s): 田原 聡子
  • Organizer: 筑波大学公開講座 健康と生命科学
  • Place of Presentation: 筑波大学 生命領域学際研究センター
  • Year and Date: 2014-08-01
• [Presentation] Control of allergic diseases by regulation of mast cell activation (2013)
  • Author(s): Tahara-Hanaoka S, et. al.
  • Organizer: JST-CREST国際シンポジウムFrontiers in Immunology & Inflammation
  • Place of Presentation: 一橋記念講堂(東京)
  • Year and Date: 2013-02-12
• [Presentation] Involvement of an inhibitory immunoglobulin-like receptor Allergin-1 in the pathogenesis of house dust mite-induced airway hyperreaction (2012)
  • Author(s): Hi to mi K, et. al.
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会磁場(兵庫)
  • Year and Date: 2012-12-07
• [Presentation] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor (2012)
  • Author(s): Nakahashi-Oda C, et. al.
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会磁場(兵庫)(招待講演)
  • Year and Date: 2012-12-06
• [Presentation] Functional analysis of an inhibitory receptor on human primary mast cell (2012)
  • Author(s): Nagai K, et. al.
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会磁場(兵庫)
  • Year and Date: 2012-12-06
• [Presentation] MAIR-II (CD300d) on inflammatory monocytes amplifies TLR4-mediated cell migration to protect from polymicrobial sepsis (2012)
  • Author(s): Totsuka N, et. al.
  • Organizer: 第41回日本免疫学会
  • Place of Presentation: 神戸国際会磁場(兵庫)
  • Year and Date: 2012-12-05
• [Presentation] 第11回免疫学セミナー (2012)
  • Author(s): 田原聡子
  • Organizer: 獨協医科大学医学部免疫学講座
  • Place of Presentation: 獨協医科大学医学部免疫学講座(栃木)(招待講演)
  • Year and Date: 2012-07-17
• [Presentation] Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor (2012)
  • Author(s): Nakhashi-Oda C, et. al.
  • Organizer: 9th International Conference on Innate Immunity
  • Place of Presentation: Rodos Palace Conference Center, Ixia, Rhodes, Greece
  • Year and Date: 2012-06-27
• [Presentation] Involvement of CD300a in the pathogenesis of DSS-induced colitis.
  • Author(s): Totsuka N, Kim YG, Tahara-Hanaoka S, Nakahashi-Oda C, Honda S, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Fca/mR (CD351) regulates inflammatory responses of marginal zone B cells against experimental septic shock.
  • Author(s): Honda S, Yoshizawa Y, Sato K, Fujimoto M, Nakahashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Identification and characterization of a novel CD300 molecule, CD300H.
  • Author(s): Niizuma K, Tahara-Hanaoka S, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Allergin-1 short-form 1 is dominantly expressed on human primary mast cells and inhibits FceRI-mediated actibation.
  • Author(s): Nagai K, Tahara-Hanaoka S, Kanemaru K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Seven color flow cytometry analyses of Allergin-1 expression and function on human primary bronchoalveolar and nasal mast cells.
  • Author(s): Nagai K, Tahara-Hanaoka S, Shibuya A.
  • Organizer: 15th International Congress of Immunology. Mico Milano Congressi
  • Place of Presentation: Milan, Italy
• [Book] アレルギー反応を抑制する新しい受容体, Allergin-1 (2014)
  • Author(s): 田原 聡子、渋谷 彰
  • Publisher: アレルギー 62(12)
• [Book] マスト細胞を標的としたアレルギー疾患制御 (2013)
  • Author(s): 金丸 和正、田原 聡子、渋谷 彰
  • Publisher: 炎症と免疫 22(1)
• [Book] 抑制性レセプターによるアレルギー・炎症制御 (2013)
  • Author(s): 小田 ちぐさ、田原 聡子、渋谷 彰
  • Publisher: 細胞工学 32(12):
• [Book] MAIR-II/DAP12によるB細胞活性化の制御 (2013)
  • Author(s): 田原 聡子、渋谷 彰
  • Publisher: 臨床免疫・アレルギー科 60(2):
• [Book] 新しいアレルギー抑制分子，Allergin-1 (2013)
  • Author(s): 田原 聡子
  • Publisher: 週刊医学のあゆみ（渋谷彰 企画）245(3):
• [Remarks] 筑波大学 免疫学研究室
  • URL: http://immuno-tsukuba.com/index.html
• [Remarks]
  • URL: http://www.tulips.tsukuba.ac.jp/dspace/handle/2241/101768
• [Patent(Industrial Property Rights)] 活性調節剤、これを含有する医薬品、CD300a遺伝子欠損マウスの使用および抗CD300a抗体 (2012)
  • Inventor(s): 渋谷彰、小田ちぐさ、田原聡子、鍋倉宰、カンカーナム ガマゲ サナトウ ウダヤンガ、三木春香、飯野秀一
  • Industrial Property Rights Holder: 筑波大学
  • Filing Date: 2012-11-07
  • Overseas