Circulating CD27-CD4+T cells in patients with asthma

• Project/Area Number: 25461167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Juntendo University
• Principal Investigator: Harada Norihiro 順天堂大学, 医学部, 准教授 (10465065)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 気管支喘息 / 補助シグナル分子 / 自然リンパ球 / バイオマーカー / Th2 / CD27 / ペリオスチン / テネイシンC

Outline of Final Research Achievements

We have repoted an important role for CD27 in the development of pathogenic Th2 cells in a murine model of allergic lung inflammation. Moreover, not only Th2 cells but also a variety of innate subsets of lymphoid cells such as innate lymphoid cells (ILCs), and mucosal-associated invariant T (MAIT) cells are involved in asthma and may have important effector functions in asthmatics. In the present study, we investigated whether the CD27-CD4+T cells ILCs and MAIT cells in the peripheral blood of patients with asthma would be associated with clinical asthma parameters. There were no significant differences in the frequencies of CD27-CD4+T cells, ILCs and MAIT cells between the asthma severity groups. The percentage of activated NK cells, group 1 ILCs, group 2 ILCs, group 3 ILCs and MAIT cells in the peripheral blood of asthmatics were positively correlated with each other, and may orchestrate immune responses, but not behave as an individual population, in asthmatic airway inflammation.

Research Products

• [Journal Article] Evaluation of switching low-dose inhaled corticosteroid to pranlukast for step-down therapy in well-controlled patients with mild persistent asthma. (2015)
  • Author(s): Harada, S., N. Harada, Y. Itoigawa, Y. Katsura, F. Kasuga, A. Ishimori, F. Makino, J. Ito, R. Atsuta, and K. Takahashi.
  • Journal Title: Journal of Asthma Volume: 53 Issue: 2 Pages: 207-212
  • DOI: 10.3109/02770903.2015.1087556
  • Peer Reviewed
• [Journal Article] Characteristics of alveolar macrophages from murine models of OVA-induced allergic airway inflammation and LPS-induced acute airway inflammation (2015)
  • Author(s): 1)Katsura Y, Harada N, Harada S, Ishimori A, Makino F, Ito J, Kamachi F, Okumura K, Akiba H, Atsuta R, Takahashi K
  • Journal Title: Experimental Lung Research Volume: 41 Issue: 7 Pages: 370-382
  • DOI: 10.3109/01902148.2015.1044137
  • Peer Reviewed
• [Journal Article] ICOS promotes group 2 innate lymphoid cell activation in lungs (2015)
  • Author(s): Kamachi F, Isshiki T, Harada N, Akiba H, Miyake S
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 463 Issue: 4 Pages: 739-745
  • DOI: 10.1016/j.bbrc.2015.06.005
  • Peer Reviewed / Open Access
• [Journal Article] TWEAK enhances TGF-beta-induced epithelial-mesenchymal transition in human bronchial epithelial cells. (2015)
  • Author(s): Itoigawa, Y., N. Harada, S. Harada, Y. Katsura, F. Makino, J. Ito, F. Nurwidya, M. Kato, F. Takahashi, R. Atsuta, and K. Takahashi.
  • Journal Title: Respir Res Volume: 16 Issue: 1 Pages: 48-48
  • DOI: 10.1186/s12931-015-0207-5
  • Peer Reviewed / Open Access
• [Journal Article] Real-time trafficking of PEGylated liposomes in the rodent focal brain ischemia analyzed by positron emission tomography (2014)
  • Author(s): Fukuta T, Ishii T, Asai T, Nakamura G, Takeuchi Y, Sato A, Agato Y, Shimizu K, Asai S, Fukumoto D, Harada N, Tsukada H, Kawaguchi AT, Oku N
  • Journal Title: Artificial organs Volume: 38 Issue: 8 Pages: 662-6
  • DOI: 10.1111/aor.12350
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comparison of exhaled nitric oxide levels measured by two offline methods and the NO breath® method in Japan (2014)
  • Author(s): Ito J, Tsuburai T, Atsuta R, Watai K, Fukuhara M, Hayashi H, Minami T, Tanimoto H, Oshikata C, Sekiya K, Tsurikizawa N, Fukutomi Y, Harada N, Maeda Y, Mori A, Hasegawa M, Taniguchi M, Takahashi K, Akiyama K
  • Journal Title: アレルギー Volume: 63 Pages: 1241-1249
  • Peer Reviewed
• [Journal Article] FOT(Forced Oscillation technique)を用いた気道可逆性の検討 (2014)
  • Author(s): 桂蓉子，熱田了，原田園子，松野圭，春日文子，糸魚川幸成，石森絢子，牧野文彦，伊藤潤，長島修，梶山雄一郎，原田紀宏，高橋和久
  • Journal Title: 臨床呼吸生理 Volume: 46 Pages: 23-26
• [Journal Article] OX40 ligand regulates splenic CD8- dendritic cell-induced Th2 responses in vivo. (2014)
  • Author(s): Kamachi F, Harada N, Usui Y, Sakanishi T, Ishii N, Okumura K, Miyake S, Akiba H
  • Journal Title: Biochem Biophys Res Commun Volume: 444 Issue: 2 Pages: 235-240
  • DOI: 10.1016/j.bbrc.2014.01.060
  • Peer Reviewed
• [Presentation] TWEAK induced chemokine, MCP-1, RANTES and IL-8 production in human bronchial epithelial cells (2016)
  • Author(s): K. Matsuno, N. Harada, A. Ishimori, S. Harada, T. Takeshige, J. Ito, R. Atsuta, K. Takahashi
  • Organizer: American Thoracic Society (ATS) International Conference 2016
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] 気管支喘息症例における末梢血中自然リンパ球MAIT細胞の解析 (2016)
  • Author(s): 石森絢子，原田紀宏，原田園子，松野圭，竹重智仁，中村愛，牧野文彦，伊藤潤，熱田了，千葉麻子，出原賢治，三宅幸子，高橋和久
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市、京都府
  • Year and Date: 2016-04-08
• [Presentation] 気管支喘息症例における血清テネイシンC値 (2016)
  • Author(s): 浅地美奈，原田紀宏，原田園子，石森絢子，松野圭，田辺悠記，笹野仁史，桂蓉子，牧野文彦，伊藤潤，飛野和則，熱田了，出原賢治，高橋和久
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市、京都府
  • Year and Date: 2016-04-08
• [Presentation] 気道上皮細胞におけるTGF-βが誘導するEMTとTWEAKの関連 (2016)
  • Author(s): 糸魚川幸成，原田紀宏，石森絢子，原田園子，桂蓉子，松野圭，竹重智仁，田辺悠記，笹野仁史，牧野文彦，伊藤潤，長島修，熱田了，高橋和久
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市、京都府
  • Year and Date: 2016-04-08
• [Presentation] TWEAK Induced Chemokine, MCP-1, RANTES and IL-8 Production by Human Bronchial Epithelial Cells (2016)
  • Author(s): 松野圭，原田紀宏，石森絢子，原田園子，竹重智仁，田辺悠記，笹野仁史，桂蓉子，糸魚川幸成，牧野文彦，伊藤潤，長島修，熱田了，高橋和久
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市、京都府
  • Year and Date: 2016-04-08
• [Presentation] 喘息外来患者におけるチオトロピウムの長期的な臨床効果 (2016)
  • Author(s): 5.伊藤潤，原田紀宏，牧野文彦，桂蓉子，石森絢子，糸魚川幸成，春日文子，松野圭，梶山雄一郎，長島修，熱田了，高橋和久
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館、京都市、京都府
  • Year and Date: 2016-04-08
• [Presentation] 気管支喘息における末梢血中mucosal-associated invariant T細胞の解析 (2015)
  • Author(s): 原田園子，原田紀宏，石森絢子，桂蓉子，松野圭，竹重智仁，糸魚川幸成，牧野文彦，伊藤潤，熱田了，千葉麻子，出原賢治，三宅幸子，高橋和久
  • Organizer: 第25回国際喘息学会日本・北アジア部会
  • Place of Presentation: ホテルニューグランド、横浜市、神奈川県
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] 気管支喘息における血清テネイシンCの解析 (2015)
  • Author(s): 原田紀宏，原田園子，石森絢子，松野圭，竹重智仁，田辺悠記，笹野仁史，桂蓉子，糸魚川幸成，牧野文彦，伊藤潤，熱田了，出原賢治，高橋和久
  • Organizer: 第25回国際喘息学会日本・北アジア部会
  • Place of Presentation: ホテルニューグランド、横浜市、神奈川県
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] 長時間作用型抗コリン薬の長期的な臨床効果 (2015)
  • Author(s): 伊藤潤，原田紀宏，牧野文彦，桂蓉子，石森絢子，糸魚川幸成，松野圭，竹重智仁，田辺悠記，笹野仁史，梶山雄一郎，長島修，熱田了，高橋和久
  • Organizer: 第25回国際喘息学会日本・北アジア部会
  • Place of Presentation: ホテルニューグランド、横浜市、神奈川県
  • Year and Date: 2015-09-03
• [Presentation] 当院における気管支喘息に対するオマリズマブの長期臨床効果の検討 (2015)
  • Author(s): 松野圭，原田紀宏，桂蓉子，原田園子，伊藤潤，石森絢子，糸魚川幸成，牧野文彦，竹重智仁，梶山雄一郎，長島修，熱田了，高橋和久
  • Organizer: 第25回国際喘息学会日本・北アジア部会
  • Place of Presentation: ホテルニューグランド、横浜市、神奈川県
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] キチン誘導性気道炎症におけるPGE2産生と肺胞マクロファージの役割 (2015)
  • Author(s): 石森絢子，原田紀宏，桂蓉子，原田園子，松野圭，竹重智仁，田辺悠記，笹野仁史，糸魚川幸成，牧野文彦，伊藤潤，長島修，熱田了，高橋和久
  • Organizer: 第25回国際喘息学会日本・北アジア部会
  • Place of Presentation: ホテルニューグランド、横浜市、神奈川県
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] OVA誘導性喘息モデルマウスとLPS誘導性急性肺障害モデルマウスの肺胞マクロファージにおけるPGE2産生誘導 (2015)
  • Author(s): 石森絢子，原田紀宏，桂蓉子，原田園子，松野圭，竹重智仁，田辺悠記，笹野仁史，糸魚川幸成，牧野文彦，伊藤潤，長島修，熱田了，高橋和久
  • Organizer: 第25回国際喘息学会日本・北アジア部会
  • Place of Presentation: ホテルニューグランド、横浜市、神奈川県
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] 気道上皮細胞におけるTWEAKのTGF-βが誘導するEMTへの影響 (2015)
  • Author(s): 糸魚川幸成，原田紀宏，石森絢子，原田園子，桂蓉子，松野圭，竹重智仁，田辺悠記，笹野仁史，牧野文彦，伊藤潤，長島修，熱田了，高橋和久
  • Organizer: 第25回国際喘息学会日本・北アジア部会
  • Place of Presentation: ホテルニューグランド、横浜市、神奈川県
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] 喘息モデルマウスと急性肺障害モデルマウスにおける肺胞マクロファージの解析 (2015)
  • Author(s): 原田紀宏，桂蓉子，石森絢子，原田園子，松野圭，竹重智仁，田辺悠記，笹野仁史，牧野文彦，伊藤潤，梶山雄一郎，長島修，熱田了，高橋和久
  • Organizer: 第25回国際喘息学会日本・北アジア部会
  • Place of Presentation: ホテルニューグランド、横浜市、神奈川県
  • Year and Date: 2015-09-03
  • Int'l Joint Research
• [Presentation] Anti-TIM-4 mAb ameliorates allergic lung inflammation (2014)
  • Author(s): F. Kamachi, N. Harada, J. Ito, K. Takahashi, K. Okumura, S. Miyake, H. Akiba
  • Organizer: The Multifaceted Roles of Type 2 Immunity
  • Place of Presentation: Belgium
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] アスピリン負荷試験における呼気一酸化窒素濃度・鼻腔内一酸化窒素濃度測定の有用性の検討 (2014)
  • Author(s): 伊藤潤, 谷口正実, 粒来崇博, 渡井健太郎, 福原正憲, 林浩昭, 南崇史, 三井千尋,押方智也子, 関谷潔史, 釣木澤尚実, 福冨友馬, 原田紀宏, 前田裕二, 森晶夫, 熱田了, 高橋和久, 秋山一男
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都
  • Year and Date: 2014-05-09 – 2014-05-11
• [Presentation] 長期Omalizumab投与時の喘息患者におけるFree IgE (2014)
  • Author(s): 熱田了，伊藤玲子，権寧博，原田園子，石森絢子，桂蓉子，糸魚川幸成，牧野文彦，伊藤潤，原田紀宏，橋本修，高橋和久
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都
  • Year and Date: 2014-05-09 – 2014-05-11
• [Presentation] フェノタイプからみたマウス肺胞マクロファージの解析 (2014)
  • Author(s): 桂蓉子，原田紀宏，原田園子，牧野文彦，伊藤潤，糸魚川幸成，松野圭，春日文子，石森絢子，長島修，蒲池史卓，秋葉久弥，熱田了，高橋和久
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] 喘息患者における7-8年後の呼気一酸化窒素と呼吸機能の変化 (2014)
  • Author(s): 伊藤潤, 谷口正実, 粒来崇博, 渡井健太郎, 林浩昭, 南崇史, 三井千尋, 谷本英則, 押方智也子, 関谷潔史, 釣木澤尚実, 福冨友馬, 原田紀宏, 前田裕二, 森晶夫, 熱田了, 高橋和久, 秋山一男
  • Organizer: 第54回日本呼吸器学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] Soluble form of TIM-4 regulates mast cell activation by binding to LMIR5 and TIM-3 (2013)
  • Author(s): Fumitaka Kamachi, Norihiro Harada, Chiharu Nishiyama, Kumi Izawa, Jiro Kitaura, Ko Okumura, Sachiko Miyake, Hisaya Akiba.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] 成人気管支喘息における心理社会的背景と唾液中ストレスマーカーの検討 (2013)
  • Author(s): 桂蓉子, 熱田了, 原田園子, 糸魚川幸成, 原田紀宏, 高橋和久
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: ホテルニューオータニ（東京）
• [Presentation] アドヒアランス問診票；ASK20の喘息患者に対する有用性とアドヒアランスが呼気NO値に与える影響 (2013)
  • Author(s): 熱田了, 原田園子, 松野圭, 春日文子, 桂蓉子, 石森絢子, 糸魚川幸成, 牧野文彦, 伊藤潤, 梶山雄一郎, 長島修, 原田紀宏, 高橋和久
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: ホテルニューオータニ（東京）
• [Presentation] A switching low dose inhaled corticosteroid to pranlukast in mild persistent asthma (2013)
  • Author(s): Fumiko Kasuga, Sonoko Harada, Norihiro Harada, Fumihiko Makino, Jun Ito, Yukinari Itoigawa, Yoko Katsura, Ayako Ishimori, Kei Matsuno, Osamu Nagashima, Ryo Atsuta and Kazuhisa Takahashi.
  • Organizer: 18th congress of the Asian Paciffic Society of Respirology
  • Place of Presentation: パシフィコ横浜
• [Presentation] Examining how FM/BUD affects bronchodilatation and the time taken for effects to appear (2013)
  • Author(s): Yukinari Itoigawa, Ryo Atsuta, Sonoko Harada, Yoko Katsura, Kei Matsuno, Ayako Ishimori, Fumihiko Makino, Jun Ito, Osamu Nagashima, Norihiro Harada, Kazuhisa Takahashi.
  • Organizer: 18th congress of the Asian Paciffic Society of Respirology
  • Place of Presentation: パシフィコ横浜
• [Presentation] The effect of chitin on IL-1β production by alveolar macrophage (2013)
  • Author(s): Yoko Katsura, Norihiro Harada, Sonoko Harada, Yukinari Itoigawa, Kei Matsuno, Ayako Ishimori, Osamu Nagashima, Fumihiko Makino, Jun Ito, Ryo Atsuta and Kazuhisa Takahashi.
  • Organizer: 18th congress of the Asian Paciffic Society of Respirology
  • Place of Presentation: パシフィコ横浜
• [Presentation] TWEAK enhances TGF-β-induced epithelial-mesenchymal transition in BEAS-2B human bronchial epithelial cells. (2013)
  • Author(s): Yukinari Itoigawa, Norihiro Harada, Sonoko Harada, Yoko Katsura, Kei Matsuno, Ayako Ishimori, Osamu Nagashima, Fumihiko Makino, Jun Ito, Ryo Atsuta, Kazuhisa Takahashi.
  • Organizer: 18th congress of the Asian Paciffic Society of Respirology
  • Place of Presentation: パシフィコ横浜
• [Presentation] Characteristics of alveolar macrophages from murine model of OVA-induced and LPS-induced airway inflammation (2013)
  • Author(s): Norihiro Harada, Yoko Katsura, Sonoko Harada, Fumihiko Makino, Jun Ito, Yukinari Itoigawa, Kei Matsuno, Fumiko Kasuga, Ayako Ishimori, Osamu Nagashima, Fumitaka Kamachi, Hisaya Akiba, Ryo Atsuta, and Kazuhisa Takahashi
  • Organizer: 18th congress of the Asian Paciffic Society of Respirology
  • Place of Presentation: パシフィコ横浜
• [Presentation] キチンによる肺胞マクロファージのIL-1β産生の誘導 (2013)
  • Author(s): 桂蓉子，原田紀宏，松野圭，石森絢子，糸魚川幸成，牧野文彦，伊藤潤，長島修，熱田了，高橋和久
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] ASK20(Adherence Starts with Knowledge)を用いたadherence向上へのアプローチ (2013)
  • Author(s): 熱田了，原田園子，松野圭，春日文子，石森絢子，桂蓉子，糸魚川幸成，牧野文彦，伊藤潤，梶山雄一郎，長島修，原田紀宏，高橋和久
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京）