The role of Foxp3+ CD3- innate cells in allergic airway inflammation

• Project/Area Number: 26461486
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Chiba University
• Principal Investigator: TAKATORI Hiroaki 千葉大学, 医学部附属病院, 助教 (30568225)
• Co-Investigator(Kenkyū-buntansha): 玉地 智宏 千葉大学, 大学院医学研究院, 助教 (20456015) ; 廣瀬 晃一 千葉大学, 大学院医学研究院, 准教授 (90400887)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アレルギー性気道炎症 / 自然リンパ球 / T-bet / 自然型アレルギー性炎症 / IL-33 / 制御性免疫細胞

Outline of Final Research Achievements

In this study, we examined the role of Foxp3+ CD3- innate cells and the new mechanism to regulate allergic inflammation.
a) B220, MHC classII, and CCR6 were expressed on Foxp3+ CD3- cells from spleen of hCD2-Foxp3 reporter mice. b) IAIE+ Foxp3+ CD3- cells in the lungs of hCD2-Foxp3 reporter mice were increased after intranasally papain administration. Those results suggest that Foxp3+ CD3- cells were induced in the lungs to regulate allergic airway inflammation without anti-inflammatory cytokine secretion.

Research Products

• [Journal Article] T-bet inhibits innate lymphoid cell-mediated eosinophilic airway inflammation by suppressing IL-9 production (2017)
  • Author(s): Matsuki A, Takatori T, Makita S, Yokota M, Tamachi T, Suto A, Suzuki K, Hirose K, Nakajima H
  • Journal Title: J. Allergy Clin. Immunol Volume: 印刷中 Issue: 4 Pages: 31023-31025
  • DOI: 10.1016/j.jaci.2016.08.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dectin-1 Plays an Important Role in House Dust Mite-Induced Allergic Airway Inflammation through the Activation of CD11b+ Dendritic Cells. (2016)
  • Author(s): Ito T, Hirose K, Norimoto A, Tamachi T, Yokota M, Saku A, Takatori H, Saijo S, Iwakura Y, Nakajima H.
  • Journal Title: J Immunol. Volume: 198 Pages: 61-70
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Helios enhances regulatory T cell function in cooperation with Foxp3 (2015)
  • Author(s): Takatori H, Kawashima H, Matsuki A, Meguro K, Tanaka S, Iwamoto T, Sanayama Y, Nishikawa N, Tamachi T, Ikeda K, Suto A, Suzuki K, Kagami S, Hirose K, Kubo M, Hori S, Nakajima H
  • Journal Title: Arthritis Rheumatol Volume: 67 Issue: 6 Pages: 1491-502
  • DOI: 10.1002/art.39091
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MMP12 is produced by M2 monocytes-macrophages and plays important roles in the development of contact hypersensitivity (2015)
  • Author(s): Nakagomi D, Suzuki K, Meguro K, Hosokawa J, Tamachi T, Takatori H, Suto A, Matsue H, Ohara O, Nakayama T, Shimada S, Nakajima H
  • Journal Title: J Allergy Clin Immunol Volume: 135 Issue: 5 Pages: 1397-400
  • DOI: 10.1016/j.jaci.2014.10.055
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Roles of B Cell Leukemia/Lymphoma 3 in the development of T follicular helper cells and the pathogenesis of rheumatoid arthritis. (2015)
  • Author(s): Meguro, K., Suzuki, K., Hosokawa, J., Sanayama, Y., Tanaka, S., Furuta, S., Ikeda, K., Takatori, H, Suto, A., Sakamoto, A., Ohara, O., Nakajima, H.
  • Journal Title: Arthritis & Rheumatology Volume: 67 Issue: 10 Pages: 2651-60
  • DOI: 10.1002/art.39266
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] IL-21-producing c-Maf-expressing CD4+ T cells induce effector CD8+ T cells and enhance autoimmune inflammation in scurfy mice (2014)
  • Author(s): Iwamoto T, Suto A, Tanaka S, Takatori H, Suzuki K, Iwamoto I, Nakajima H
  • Journal Title: Arthritis Rheumatol Volume: (巻不明) Issue: 8 Pages: 2079-2090
  • DOI: 10.1002/art.38658
  • Peer Reviewed
• [Journal Article] Sox5 and c-Maf cooperatively induce Th17 cell differentiation via ROR gamma t induction as downstream targets of Stat3 (2014)
  • Author(s): Tanaka S, Suto A, Iwamoto T, Kashiwakuma D, Kagami S, Suzuki K, Takatori H, Tamachi T, Hirose K, Onodera A, Suzuki J, Ohara O, Yamashita M, Nakayama T, Nakajima H
  • Journal Title: J Exp Med Volume: 211 Issue: 9 Pages: 1857-1874
  • DOI: 10.1084/jem.20130791
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of p53 in systemic autoimmune diseases. (2014)
  • Author(s): Takatori H, Kawashima H, Suzuki K, Nakajima H.
  • Journal Title: Critical Reviews in Immunology Volume: 34 Pages: 509-516
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 制御性T細胞におけるIkarosファミリー分子Heliosの発現機構とその役割 (2016)
  • Author(s): 高取宏昌，川島広捻，中島裕史
  • Organizer: 第44回日本臨床免疫学会
  • Place of Presentation: 京王プラザ（東京都新宿区）
  • Year and Date: 2016-09-08
• [Presentation] T-bet regulates IL-33-induced airway inflammation by suppressing IL-9 production from innate lymphoid cells (2016)
  • Author(s): Matsuki A, Takatori H, Makita S, Yokota M,Tamachi T,Suto A,Suzuki K,Hirose K,Nakajima.
  • Organizer: The International Congress of Immunology
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2016-08-22
  • Int'l Joint Research
• [Presentation] T-betはILC2によるIL-9産生を抑制し，IL-33誘導性気道炎症を制御する (2016)
  • Author(s): 松木彩子，高取宏昌，牧田荘平，玉地智宏，廣瀬晃一，中島裕史
  • Organizer: 第65回日本アレルギー学会総会・学術集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-06-18
• [Presentation] HeliosはFoxp3と協調して制御性T細胞の機能を増強する。 (2015)
  • Author(s): 高取宏昌、川島広捻、中島裕史
  • Organizer: 第80回日本インターフェロン・サイトカイン研究会
  • Place of Presentation: 東京工業大学大岡山キャンパス蔵前会館蔵前ホール（東京都・目黒区）
  • Year and Date: 2015-07-17
• [Presentation] ヒトCD4+ T細胞のサイトカイン発現制御におけるHeliosの役割 (2014)
  • Author(s): 高取宏昌、川島広稔、眞山快枝、池田啓、中島裕史
  • Organizer: 日本リウマチ学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2014-04-24 – 2014-04-26