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Role of epithelial glycosylation in the development of allergic airway inflammation

Research Project

Project/Area Number 17K09645
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionChiba University

Principal Investigator

Hirose Koichi  千葉大学, 大学院医学研究院, 特任教授 (90400887)

Co-Investigator(Kenkyū-buntansha) 玉地 智宏  千葉大学, 大学院医学研究院, 特任講師 (20456015)
岩田 有史  千葉大学, 大学院医学研究院, 助教 (90436353)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアレルギー性気道炎症 / 気道上皮細胞 / フコシル化 / Fut2 / 補体 / 単球由来樹状細胞 / 気道上皮フコシル化 / 補体経路 / IL-13 / STAT6 / 気管支喘息 / 糖鎖修飾 / フコース転移酵素 / Th2細胞 / 起動上皮細胞
Outline of Final Research Achievements

One of the pathognomonic features of asthma is epithelial hyperproduction of mucus which is composed of a series of glycoproteins; however, it remains unclear how glycosylation is induced in asthmatic lung epithelial cells and how glycan residues play a role in the pathogenesis of asthma. Using lectin micro-array, we found that upon allergen inhalation, lung epithelial cells were heavily alpha(1,2)fucosylated by fucosyltransferase 2 (Fut2). Importantly, Fut2-deficient mice (Fut2-/- mice) exhibited significantly attenuated eosinophilic inflammation, airway hyperresponsiveness and significantly reduced levels of C3a and impaired accumulation of C3a receptor-expressing monocyte-derived dendritic cells (Mo-DCs) in the lung of HDM-induced allergic asthma model mice. Taken together, these results suggest that Fut2 induces epithelial fucosylation and exacerbates airway inflammation in asthma in part via C3a production and Mo-DC accumulation in the lung.

Academic Significance and Societal Importance of the Research Achievements

気管支喘息の臨床的特徴の一つに気道における粘液過剰産生が含まれること、またこの粘液中には多くの糖タンパク質が存在することは古くから知られていたが、糖鎖修飾がアレルギー性炎症にいかなる働きを持つかは不明であった。本研究ではアレルギー性気道炎症により誘導される糖鎖修飾を網羅的に解析し、惹起された糖鎖修飾が如何にして炎症を増悪させるかを明らかにした。
本研究により気管支喘息の新たな病態が明らかにされた。これらの知見を応用することによって、既存治療では十分な治療効果が得られていない喘息患者に対する新たな治療機軸の確立が可能となる可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017 Other

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Journal Article] Fucosyltransferase 2 induces lung epithelial fucosylation and exacerbates house dust mite-induced airway inflammation.2019

    • Author(s)
      Saku A, Hirose K, Ito T, Iwata A, Sato T, Kaji H, Tamachi T, Suto A, Goto Y, Domino SE, Narimatsu H, Kiyono H, Nakajima H
    • Journal Title

      J Allergy Clin Immunol.

      Volume: 144(3) Issue: 3 Pages: 698-709

    • DOI

      10.1016/j.jaci.2019.05.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bidirectional roles of IL-22 in the pathogenesis of allergic airway inflammation2019

    • Author(s)
      Ito T, Hirose K, Nakajima H.
    • Journal Title

      Allergology International

      Volume: 68 Issue: 1 Pages: 4-8

    • DOI

      10.1016/j.alit.2018.10.002

    • NAID

      130007557957

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-21 enhances mast cell accumulation in the intestine and exacerbates the development of experimental food allergy.2019

    • Author(s)
      Kono K, Hirose K, Makita S, Kageyama T, Tamachi T, Saku A, Suto A, Suzuki K, Nakajima H.
    • Journal Title

      Clin Exp Allergy.

      Volume: 49(11) Issue: 11 Pages: 1523-1526

    • DOI

      10.1111/cea.13473

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mice lacking fucosyltransferase 2 show reduced innate allergic inflammation in the airways.2019

    • Author(s)
      Saku A, Suehiro KI, Nakamura K, Nishimura N, Yokota M, Hirose K, Nakajima H.
    • Journal Title

      Allergy.

      Volume: - Issue: 5 Pages: 1253-1256

    • DOI

      10.1111/all.14101

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sox12 promotes T reg differentiation in the periphery during colitis.2018

    • Author(s)
      anaka S, Suto A, Iwamoto T, Kageyama T, Tamachi T, Takatori H, Suzuki K, Hirose K, Ohara O, Lefebvre V, Nakajima H.
    • Journal Title

      J Exp Med.

      Volume: 215 Issue: 10 Pages: 2509-2519

    • DOI

      10.1084/jem.20172082

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Eosinophilic vasculitis affecting multiple middle-sized arteries in a patient with Kimura's disease: A case report and literature review2018

    • Author(s)
      Furuya H, Ikeda K, Suzuki J, Suzuki K, Nakamura K, Furuta S, Tamachi T, Suzuki K, Hirose K, Nakajima H.
    • Journal Title

      Allergology International

      Volume: 67 Issue: Supplement.1 Pages: S45-S47

    • DOI

      10.1016/j.alit.2018.04.010

    • NAID

      130007485201

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles of IL-22 in allergic airway inflammation in mice and humans2018

    • Author(s)
      Hirose Koichi、Ito Takashi、Nakajima Hiroshi
    • Journal Title

      Int Immunol.

      Volume: in press Issue: 9 Pages: 413-418

    • DOI

      10.1093/intimm/dxy010

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles of Dectin-1 in Allergic Airway Inflammation.2017

    • Author(s)
      Hirose K, Ito T, Nakajima H.
    • Journal Title

      Crit Rev Immunol.

      Volume: 37 Issue: 1 Pages: 15-21

    • DOI

      10.1615/critrevimmunol.2017024718

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] IL-22 induces Reg3γ and inhibits allergic inflammation in house dust mite-induced asthma models.2017

    • Author(s)
      Ito T, Hirose K, Saku A, Kono K, Takatori H, Tamachi T, Goto Y, Renauld JC, Kiyono H, Nakajima H.
    • Journal Title

      J Exp Med.

      Volume: 214 Issue: 10 Pages: 3037-3050

    • DOI

      10.1084/jem.20162108

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Key players beyond the Th2 cell pathway2017

    • Author(s)
      Hirose K, Tamachi T, Iwata A, Nakajima H
    • Journal Title

      Immunol Rev

      Volume: 印刷中 Issue: 1 Pages: 145-161

    • DOI

      10.1111/imr.12540

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dectin-1 plays a critical role in HDM-induced PGE<sub>2</sub> production in macrophages2017

    • Author(s)
      Ito T, Hirose K, Norimoto A, Saku A, Nakajima H.
    • Journal Title

      Allergology International

      Volume: 66 Issue: Supplement.1 Pages: S44-S46

    • DOI

      10.1016/j.alit.2017.05.001

    • NAID

      130006182296

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SAPHO syndrome-like presentation of disseminated nontuberculous mycobacterial infection in a case with neutralizing anti-IFNγ autoantibody.2017

    • Author(s)
      Furuya H, Ikeda K, Miyachi K, Nakamura K, Suzuki K, Furuta S, Tamachi T, Hirose K, Sakagami T, Nakajima H.
    • Journal Title

      Rheumatology (Oxford)

      Volume: 印刷中 Issue: 7 Pages: 1241-1243

    • DOI

      10.1093/rheumatology/kex089

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] IκBNS induces Muc5ac expression in epithelial cells and causes airway hyperresponsiveness in murine asthma models2017

    • Author(s)
      Yokota M, Tamachi T, Yokoyama Y, Maezawa Y, Takatori T, Suto A, Suzuki K, Hirose K, Takeda K, Nakajima H
    • Journal Title

      Allergy

      Volume: 印刷中 Issue: 7 Pages: 13079-13079

    • DOI

      10.1111/all.13079

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] コーヒー(green coffee bean(GCB))焙煎による1型アレルギーの1例2018

    • Author(s)
      上原 悠治, 玉地 智宏, 策 愛子, 影山 貴弘, 岩田 有史, 鈴木 浩太郎, 廣瀬 晃一, 中島 裕史
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Fut2は気道上皮フコシル化を誘導しアレルギー性気道炎症を増悪させる2018

    • Author(s)
      策愛子, 廣瀬 晃一, 伊藤 崇, 佐藤 隆, 後藤 義幸, 清野 宏, 中島 裕史
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 食物アレルギーにおけるIL-21の役割の検討2018

    • Author(s)
      河野健太, 廣瀬 晃一, 牧田 荘平, 影山 貴弘, 玉地 智宏, 須藤 明, 中島 裕史
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 好酸球性気道炎症の病態:自然免疫と獲得免疫 IL-22によるアレルギー性気道炎症抑制機構2018

    • Author(s)
      伊藤 崇, 廣瀬 晃一, 中島 裕史
    • Organizer
      第67回日本アレルギー学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] IL-25, IL-33, TSLP2018

    • Author(s)
      廣瀬晃一
    • Organizer
      第5回総合アレルギー講習会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Lung epithelial fucosylation promotes the development of house dust mite (HDM)-induced allergic airway inflammation.2017

    • Author(s)
      SAKU Aiko, HIROSE Koichi, ITO Takashi, SATO Takashi, GOTO Yoshiyuki, KIYONO Hiroshi, NAKAJIMA Hiroshi
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] A20 (<em>Tnfaip3</em>) expressed in T cells suppresses Th2 cell-mediated allergic airway inflammation in mice2017

    • Author(s)
      TAMACHI Tomohiro, YOKOYAMA Yusuke, IWATA Arifumi, MAZAWA Yuko, MEGURO Kazuyuki, YOKOTA Masaya, TAKATORI Hiroaki, SUZUKI Kotaro, HIROSE Koichi, NAKAJIMA Hiroshi
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] IL-22 induces Reg3γ production from lung epithelial cells and inhibits allergic airway inflammation in house dust mite-induced asthma models2017

    • Author(s)
      ITO Takashi, HIROSE Koichi, GOTO Yoshiyuki, KIYONO Hiroshi, NAKAJIMA Hiroshi
    • Organizer
      the 5th Annual Meeting of the International Cytokine and Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] IL-22は気道上皮からのReg3gの産生を誘導し、チリダニ(HDM)誘導性アレルギー性気道炎症を抑制する2017

    • Author(s)
      伊藤崇、廣瀬晃一、後藤義幸、清野宏 、中島裕史
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] CD4陽性T細胞に発現するA20はTh2型アレルギー性気道炎症を抑制する2017

    • Author(s)
      横山裕亮、玉地智弘、岩田有史、前沢裕子、目黒和行、横田雅也、高取宏昌、須藤明、鈴木浩太郎、廣瀬晃一、中島裕史、本田浩章
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 播種性NTM症によりSAPHO症候群様の症状を呈した抗IFN-g抗体陽性の一例2017

    • Author(s)
      古矢裕樹、宮地万紗、鈴木一正、中村海人、古谷俊介、玉地智弘、池田啓、鈴木浩太郎、廣瀬晃一、中島裕史
    • Organizer
      第61回日本リウマチ学会総会・学術集会
    • Related Report
      2017 Research-status Report
  • [Remarks] 千葉大学大学院医学研究院 アレルギー・臨床免疫学

    • URL

      http://www.m.chiba-u.jp/dept/allergy-clin-immunol/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 千葉大学 アレルギー・臨床免疫学

    • URL

      http://www.m.chiba-u.jp/dept/allergy-clin-immunol/

    • Related Report
      2018 Research-status Report
  • [Remarks] 研究業績 千葉大学医学部附属病院 アレルギー・膠原病内科

    • URL

      http://www.m.chiba-u.jp/class/allergy/research/index.html

    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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