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Differentiation of follicular helper T cells induced by lung dendritic cells in asthma

Research Project

Project/Area Number 16K09577
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Furuhashi Kazuki  浜松医科大学, 医学部附属病院, 助教 (70759935)

Co-Investigator(Kenkyū-buntansha) 鈴木 勇三  浜松医科大学, 医学部, 助教 (00758435)
須田 隆文  浜松医科大学, 医学部, 教授 (30291397)
榎本 紀之  浜松医科大学, 医学部附属病院, 講師 (50436961)
Research Collaborator Sakurai Shogo  
Kemeny David Michael  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords濾胞性ヘルパーT細胞 / マウス喘息モデル / 肺樹状細胞 / ダニ抗原喘息モデル / 気管支喘息 / アレルゲン特異的抗体
Outline of Final Research Achievements

We found that follicular helper T cells (Tfh) increased in mediastinal lymph node and spleen using asthma mouse model with house dust mite (HDM) and ovalbumin (OVA) antigen. The antigen specific IgE and IgG1 antibodies were produced in those asthma models. We identified and purely isolated two lung dendritic cells (LDCs) subsets, which were conventional DC1 (cDC1) and DC2 (cDC2). Subsequently, we established co-culture assay with each LDC subset from OVA asthma mouse model and naive T cells from OT-II mice having OVA specific T cell receptors. As a result, we found that cDC2 induced greater frequencies of Tfh than cDC1.

Academic Significance and Societal Importance of the Research Achievements

本課題によって、喘息肺における所属リンパ節におけるTfh細胞の増加やアレルゲン特異的IgE抗体産生を確認し、さらにTfh細胞は、抗原提示細胞である肺樹状細胞サブセットの中のcDC2によって、より効率よく誘導されていることが確認できた。これらの結果は、気管支喘息の病態にTfh細胞が深く関わっていることを示唆し、気管支喘息において従来から重要と考えられていたTh2細胞などのヘルパーT細胞の他に、Tfh細胞が関与する気管支喘息の新たな病態の解明につながると考えられる。また将来、Tfh細胞の誘導を制御するようなTfh細胞をターゲットにした治療戦略が開発できる可能性も考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016

All Journal Article (13 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 13 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results)

  • [Journal Article] IL-17A Attenuates IFN-λ Expression by Inducing Suppressor of Cytokine Signaling Expression in Airway Epithelium2018

    • Author(s)
      Niwa Mitsuru、Fujisawa Tomoyuki、Mori Kazutaka、Yamanaka Katsumasa、Yasui Hideki、Suzuki Yuzo、Karayama Masato、Hozumi Hironao、Furuhashi Kazuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suzuki Tetsuro、Maekawa Masato、Suda Takafumi
    • Journal Title

      The Journal of Immunology

      Volume: 201 Issue: 8 Pages: 2392-2402

    • DOI

      10.4049/jimmunol.1800147

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differences in airway structural changes assessed by 3-dimensional computed tomography in asthma and asthma?chronic obstructive pulmonary disease overlap2018

    • Author(s)
      Niwa Mitsuru、Fujisawa Tomoyuki、Karayama Masato、Furuhashi Kazuki、Mori Kazutaka、Hashimoto Dai、Yasui Hideki、Suzuki Yuzo、Hozumi Hironao、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
    • Journal Title

      Annals of Allergy, Asthma & Immunology

      Volume: 121 Issue: 6 Pages: 704-710.e1

    • DOI

      10.1016/j.anai.2018.08.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography2018

    • Author(s)
      Karayama M, Inui N, Mori K, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
    • Journal Title

      Clin Exp Allergy

      Volume: 48 Issue: 3 Pages: 278-287

    • DOI

      10.1111/cea.13083

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prior exposure to inhaled allergen enhances anti-viral immunity and T cell priming by dendritic cells2018

    • Author(s)
      Lee DCP, Tay NQ, Thian M, Prabhu N, Furuhashi K, Kemeny DM.
    • Journal Title

      Plos One

      Volume: 13 Issue: 1 Pages: e0190063-e0190063

    • DOI

      10.1371/journal.pone.0190063

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IL-13 regulates IL-17C expression by suppressing NF-κB-mediated transcriptional activation in airway epithelial cells2018

    • Author(s)
      Yamanaka K, Fujisawa T, Kusagaya H, Mori K, Niwa M, Furuhashi K, Kono M, Hamada E, Suda T, Maekawa M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 495 Issue: 1 Pages: 1534-1540

    • DOI

      10.1016/j.bbrc.2017.11.207

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Persistent impairment on spirometry in chronic eosinophilic pneumonia: a longitudinal observation study (Shizuoka-CEP study)2017

    • Author(s)
      Suzuki Y, Oyama Y, Hozumi H, Imokawa S, Toyoshima M, Yokomura K, Nakamura H, Kuroishi S, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Koshimizu N, Yamada T, Mori K, Masuda M, Shirai T, Hayakawa H, Sumikawa M, Johkoh T, Suda T
    • Journal Title

      Ann Allergy Asthma Immunol

      Volume: 119 Issue: 5 Pages: 422-428

    • DOI

      10.1016/j.anai.2017.08.009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between fraction of exhaled nitric oxide and airway morphology assessed by three-dimensional CT analysis in asthma2017

    • Author(s)
      Nishimoto K, Karayama M, Inui N, Mori K, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 10187-10187

    • DOI

      10.1038/s41598-017-10504-w

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Utility of YKL-40 in Polymyositis/dermatomyositis-associated Interstitial Lung Disease2017

    • Author(s)
      Hozumi H, Fujisawa T, Enomoto N, Nakashima R, Enomoto Y, Suzuki Y, Kono M, Karayama M, Furuhashi K, Murakami A, Inui N, Nakamura Y, Mimori T, Suda T
    • Journal Title

      J Rheumatol

      Volume: 44 Issue: 9 Pages: 1394-1401

    • DOI

      10.3899/jrheum.170373

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blomia tropicalis allergen 5 (Blo t 5) T-cell epitopes and their ability to suppress the allergic immune response.2017

    • Author(s)
      Wong KH, Zhou Q, Prabhu N, Furuhashi K, Chua YL, Grotenbreg GM, Kemeny DM
    • Journal Title

      Immunology

      Volume: 152 Issue: 2 Pages: 344-355

    • DOI

      10.1111/imm.12772

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Priming with high and low respiratory allergen dose induces differential CD4+ T helper type 2 cells and IgE/IgG1 antibody responses in mice.2017

    • Author(s)
      Furuhashi K, Chua YL, Wong KHS, Zhou Q, Lee DCP, Liong KH, Teo GH, Hutchinson PE, Kemeny DM.
    • Journal Title

      Immunology

      Volume: 印刷中 Issue: 2 Pages: 227-238

    • DOI

      10.1111/imm.12726

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Respiratory impedance is correlated with morphological changes in the lungs on three-dimensional CT in patients with COPD.2017

    • Author(s)
      Karayama M, Inui N, Mori K, Kono M, Hozumi H, Suzuki Y, Furuhashi K, Hashimoto D, Enomoto N, Fujisawa T, Nakamura Y, Watanabe H, Suda T.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 41709-41709

    • DOI

      10.1038/srep41709

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease2017

    • Author(s)
      Enomoto Y, Suzuki Y, Hozumi H, Mori K, Kono M, Karayama M, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suzuki D, Ogawa N, Nakashima R, Mimori T, Iwashita T, Suda T
    • Journal Title

      Arthritis Res Ther

      Volume: 19 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s13075-016-1214-8

    • NAID

      120005973333

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Soluble hemoglobin scavenger receptor CD163 (sCD163) predicts mortality of community-acquired pneumonia2016

    • Author(s)
      Suzuki Y, Enomoto Y, Yokomura K, Hozumi H, Kono M, Karayama M, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Suda T
    • Journal Title

      J Infect

      Volume: 73 Issue: 4 Pages: 375-377

    • DOI

      10.1016/j.jinf.2016.07.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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