The role of new myeloid subsets in asthma

• Project/Area Number: 23790897
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Chiba University
• Principal Investigator: IWATA Arifumi 千葉大学, 医学部附属病院, 医員 (90436353)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アレルギー性気道炎症 / 樹状細胞 / アルギナーゼ / 気道過敏性 / arginase1

Research Abstract

Dendritic cells (DCs) play critical roles in determining the fate of CD4+ T cells. While previous studies have shown that CD11c+ DCs play an indispensable role in the induction of allergic airway inflammation and airway hyperreactivity (AHR) in murine asthma models, the precise roles of monocyte-derived inflammatory DCs (iDCs) in the asthmatic responses remain largely unknown. We show here that Th2 cell-mediated inflammation in murine asthma models instructs iDCs to express a part of alternatively-activated macrophage markers arginase 1 by a mechanism depending on the intrinsic expression of STAT6. Moreover, we show that iDCs under a Th2 environment play a critical role in the induction of AHR independently of allergic airway inflammation. Our results thus indicate the importance of iDCs in the induction of AHR as downstream effector cells inTh2 cell-mediated asthmatic responses.

Research Products

• [Journal Article] B and T lymphocyte attenuator inhibits LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling in innate immune cells (2013)
  • Author(s): Kobayashi Y, Iwata A, Suzuki K, Suto A, Kawashima S, Saito Y, Owada T, Kobayashi M, Watanabe N, Nakajima H.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 110(13) Pages: 5121-6
  • Peer Reviewed
• [Journal Article] Pre-dinner administration increases the efficacy of proton pump inhibitors on refractory GERD symptoms in connective tissue disease patients (2013)
  • Author(s): Iwata A, Ikeda K, Hirose K, Takatori H, Takahashi K, Sanayama Y, Tanaka S, Suto A, Nakajima H.
  • Journal Title: Mod Rheumatol Volume: 23(2) Pages: 357-64
  • NAID: 10031167710
  • Peer Reviewed
• [Journal Article] β-glucan curdlan induces IL-10-producing CD4+ T cells and inhibits allergic airway inflammation (2012)
  • Author(s): Kawashima S, Hirose K, Iwata A, Takahashi K, Ohkubo A, Tamachi T, Ikeda K, Kagami S, Nakajima H.
  • Journal Title: J Immunol Volume: 189(12) Pages: 5713-21
  • Peer Reviewed
• [Journal Article] beta-glucan Curdlan induces IL-10-producing CD4+T cells and inhibits allergic airway inflammation (2012)
  • Author(s): Kawashima S, Hirose K, Iwata A, Takahashi K, Ohkubo A, Tamachi T, Ikeda K, Kagami S, Nakajima H
  • Journal Title: J Immunol Volume: 189 Issue: 12 Pages: 5713-5721
  • DOI: 10.4049/jimmunol.1201521
  • Peer Reviewed
• [Journal Article] IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation (2011)
  • Author(s): Takahashi K, Hirose K, Kawashima S, Niwa Y, Wakashin H, Iwata A, Tokoyoda K, Renauld JC, Iwamoto I, Nakayama T, Nakajima H.
  • Journal Title: J Allergy Clin Immunol Volume: 128(5)
  • Peer Reviewed
• [Journal Article] STAT4 is required for IFN-β-induced MCP-1 mRNA expression in murine mast cells (2011)
  • Author(s): Iida K, Suzuki K, Yokota M, NakagomiD, Wakashin H, Iwata A, Kawashima H, Takatori H, Nakajima H.
  • Journal Title: Int Arch Allergy Immunol Volume: 155 Suppl1 Pages: 71-6
  • Peer Reviewed
• [Journal Article] IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation (2011)
  • Author(s): Takahashi, K., Hirose, K., Kawashima, S., Niwa, Y., Wakashin, H., Iwata, A., Tokoyoda, K., Renauland Nakad, J.-C., Iwamoto, I., Nakayama, T. Nakajima, H
  • Journal Title: J. Allergy Ciln. Immunol Volume: 128 Issue: 5 Pages: 1067-1076
  • DOI: 10.1016/j.jaci.2011.06.018
  • Peer Reviewed
• [Presentation] curdlanはIL-10産生CD4陽性T細胞を誘導し (2012)
  • Author(s): 川島沙紀、廣瀬晃一、岩田有史、高橋健太郎、加々美新一郎、中島裕史
  • Organizer: アレルギー性気道炎症を抑制する第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-29
• [Presentation] curdlanはIL-10産生CD4陽性T細胞を誘導し、アレルギー性気道炎症を抑制する (2012)
  • Author(s): 川島沙紀、廣瀬晃一、岩田有史、高橋健太郎、加々美新一郎、中島裕史
  • Organizer: 第62回日本アレルギー学会秋季学術大会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2012-11-29
• [Presentation] IL-22 attenuates IL-25 production by lung epithelial cells and inhibits antigen-induced eosinophilic airway inflammation (2012)
  • Author(s): Takahashi K, Kawashima S, Niwa Y, Iwata A, Kobayashi Y, Kagami S, Suto A, Hirose K, Watanabe N, Nakayama T, Nakajima H.
  • Organizer: The American Association of Immunologists
  • Place of Presentation: Boston, USA
  • Year and Date: 2012-05-06
• [Presentation] IL-22は気道上皮細胞によるIL-25産生を抑制し (2011)
  • Author(s): 高橋健太郎、廣瀬晃一、川島沙紀、丹羽祐輔、若新英史、岩田有史、小林芳久、常世田孝司、中山俊憲、谷口正実、秋山一男、中島裕史
  • Organizer: アレルギー性気道炎症を制御する第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-21
• [Presentation] 多発性筋炎マウスモデルにおける肥満細胞の役割の解析 (2011)
  • Author(s): 横田雅也、鈴木浩太郎、中込大樹、岩田有史、常世田好司、中山俊憲、上坂等、中島裕史
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-01-28
• [Presentation] IL-22は気道上皮細胞によるIL-25産生を抑制し、アレルギー性気道炎症を制御する (2011)
  • Author(s): 高橋健太郎, 廣瀬晃一, 川島沙紀, 丹羽祐輔, 若新英史, 岩田有史, 小林芳久, 常世田孝司, 中山俊憲, 谷口正実, 秋山一男
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Place of Presentation: 東京
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/gene/kenkyugyouseki.html