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Elucidation of unknown function of mast cells in atopic dermatitis associated with food allergy

Research Project

Project/Area Number 15K09784
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionJuntendo University

Principal Investigator

NAKANO Nobuhiro  順天堂大学, 医学(系)研究科(研究院), 助教 (30420839)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords食物アレルギー / マウスモデル / マスト細胞 / Notchシグナル / 転写調節因子 / 皮膚炎
Outline of Final Research Achievements

Intestinal mast cells are a major effector cells in food allergy. However, the functions and differentiation process of intestinal mast cells are largely unknown.
In this study, we found that the response of mast cells to TGF-β, which is an inducer of intestinal mast cell differentiation, is mediated by the transcription factor EHF. In addition, we showed that the signaling mediated by Notch receptors contributes to the differentiation of intestinal mast cells. Moreover, the study using a mouse model of food allergy demonstrated that symptoms associated with food allergy are alleviated by administration of a Notch signaling inhibitor to the mice.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (25 results)

All 2018 2017 2016 2015 Other

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 11 results,  Acknowledgement Compliant: 4 results) Presentation (11 results) Remarks (1 results)

  • [Journal Article] The CD300e molecule in mice is an immune-activating receptor.2018

    • Author(s)
      Isobe M, Izawa K, Sugiuchi M, Sakanishi T, Kaitani A, Takamori A, Maehara A, Matsukawa T, Takahashi M, Yamanishi Y, Oki T, Uchida S, Uchida K, Ando T, Maeda K, Nakano N, Yagita H, Takai T, Ogawa H, Okumura K, Kitamura T, Kitaura J.
    • Journal Title

      J Biol Chem.

      Volume: 293 Issue: 10 Pages: 3793-3805

    • DOI

      10.1074/jbc.ra117.000696

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of the ceramide-CD300f interaction in gram-negative bacterial skin infections.2018

    • Author(s)
      Maehara A, Kaitani A, Izawa K, Shiba E, Nagamine M, Takamori A, Isobe M, Uchida S, Uchida K, Ando T, Keiko M, Nakano N, Voehringer D, Roers A, Shimizu T, Ogawa H, Okumura K, Kitamura T, Kitaura J.
    • Journal Title

      J Invest Dermatol.

      Volume: 138 Issue: 5 Pages: 1221-1224

    • DOI

      10.1016/j.jid.2017.11.025

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Disrupting ceramide-CD300f interaction prevents septic peritonitis by stimulating neutrophil recruitment.2017

    • Author(s)
      Izawa K, Maehara A, Isobe M, Yasuda Y, Urai M, Hoshino Y, Ueno K, Matsukawa T, Takahashi M, Kaitani A, Shiba E, Takamori A, Uchida S, Uchida K, Maeda K, Nakano N, Yamanishi Y, Oki T, Voehringer D, Roers A, Nakae S, Ishikawa J, Kinjo Y, Shimizu T, Ogawa H, Okumura K, Kitamura T, Kitaura J
    • Journal Title

      Sci Rep.

      Volume: 7(1) Issue: 1 Pages: 4298-4298

    • DOI

      10.1038/s41598-017-04647-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <i>Clock</i>-dependent temporal regulation of IL-33/ST2-mediated mast cell response2017

    • Author(s)
      Kawauchi T, Ishimaru K, Nakamura Y, Nakano N, Hara M, Ogawa H, Okumura K, Shibata S, Nakao A
    • Journal Title

      Allergology International

      Volume: 66 Issue: 3 Pages: 472-478

    • DOI

      10.1016/j.alit.2017.02.004

    • NAID

      130005858846

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ceramide-CD300f Binding Inhibits Lipopolysaccharide-induced Skin Inflammation.2017

    • Author(s)
      Shiba E, Izawa K, Kaitani A, Isobe M, Maehara A, Uchida K, Maeda K, Nakano N, Ogawa H, Okumura K, Kitamura T, Shimizu T, Kitaura J
    • Journal Title

      J Biol Chem.

      Volume: 292 Issue: 7 Pages: 2924-2932

    • DOI

      10.1074/jbc.m116.768366

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pharmacological inhibition of Notch signaling suppresses food antigen-induced mucosal mast cell hyperplasia.2017

    • Author(s)
      Honjo A, Nakano N, Yamazaki S, Hara M, Uchida K, Kitaura J, Nishiyama C, Yagita H, Ohtsuka Y, Ogawa H, Okumura K, Shimizu T
    • Journal Title

      J Allergy Clin Immunol.

      Volume: 139 Issue: 3 Pages: 987-996

    • DOI

      10.1016/j.jaci.2016.05.046

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 腸管マスト細胞の分化と分布に対するNotchシグナルの役割と食物アレルギーへのNotchシグナルの関与2017

    • Author(s)
      中野信浩、本庄明日香、奥村康
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 67 Pages: 68-73

    • Related Report
      2016 Research-status Report
  • [Journal Article] Role of PU.1 in MHC class II Expression via CIITA Transcription in Plasmacytoid Dendritic Cells2016

    • Author(s)
      Miura R, Kasakura K, Nakano N, Hara M, Maeda K, Okumura K, Ogawa H, Yashiro T, Nishiyama C
    • Journal Title

      PLOS ONE

      Volume: 11 Issue: 4 Pages: e0154094-e0154094

    • DOI

      10.1371/journal.pone.0154094

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Notch signaling enhances FceRI-mediated cytokine production by mast cells through direct and indirect mechanisms2015

    • Author(s)
      Nakano, N., Nishiyama, C., Yagita, H., Hara, M., Motomura, Y., Kubo, M., Okumura, K., and Ogawa, H
    • Journal Title

      J. Immunol

      Volume: 194(9) Issue: 9 Pages: 4535-44

    • DOI

      10.4049/jimmunol.1301850

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Involvement of PU.1 in NFATc1 promoter function in osteoclast development2015

    • Author(s)
      Ishiyama K, Yashiro T, Nakano N, Kasakura K, Miura R, Hara M, Kawai F, Maeda K, Tamura N, Okumura K, Ogawa H, Takasaki Y, Nishiyama C
    • Journal Title

      Allergology International

      Volume: 64 Issue: 3 Pages: 241-247

    • DOI

      10.1016/j.alit.2015.01.006

    • NAID

      130005290298

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Transcription Factor Ehf Is Involved in TGF-β-Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells.2015

    • Author(s)
      Yamazaki S, Nakano N, Honjo A, Hara M, Maeda K, Nishiyama C, Kitaura J, Ohtsuka Y, Okumura K, Ogawa H, Shimizu T
    • Journal Title

      Journal of immunology

      Volume: 195(7) Issue: 7 Pages: 3427-3435

    • DOI

      10.4049/jimmunol.1402856

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of IgE-mediated allergic reactions by pharmacologically targeting the circadian clock.2015

    • Author(s)
      Nakamura Y, Nakano N, Ishimaru K, Ando N, Katoh R, Suzuki-Inoue K, Koyanagki S, Ogawa H, Okumura K, Shibata S, Nakao A
    • Journal Title

      The Journal of allergy and clinical immunology

      Volume: 137(4) Issue: 4 Pages: 1226-1235

    • DOI

      10.1016/j.jaci.2015.08.052

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TGF-βによるマスト細胞のFcεRIおよびc-Kitの発現抑制2015

    • Author(s)
      中野信浩、山﨑 晋、奥村 康
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 64(5) Pages: 429-434

    • Related Report
      2015 Research-status Report
  • [Presentation] Notchシグナルによってマスト細胞が獲得する抗原提示細胞様の形質2017

    • Author(s)
      中野信浩、西山千春、奥村康、小川 秀興
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都女子大学(京都府・京都市)
    • Year and Date
      2017-03-18
    • Related Report
      2016 Research-status Report
  • [Presentation] Notchシグナルによってマスト細胞が獲得する抗原提示細胞様の形質2017

    • Author(s)
      中野 信浩、西山 千春、奥村 康、小川 秀興
    • Organizer
      日本農芸化学会2017年度大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腸管マスト細胞の形質発現におけるNotchシグナルの寄与2017

    • Author(s)
      中野信浩、北浦次郎、西山千春、八木田秀雄、奥村康、小川秀興
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mast cells acquire intestinal antigen-presenting cell-like properties by Notch signaling2017

    • Author(s)
      Nobuhiro Nakano, Ko Okumura, Hideoki Ogawa
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Notch signaling contributes to the acquisition of an antigen-presenting cell-like phenotype in intestinal mast cells2017

    • Author(s)
      Nobuhiro Nakano, Ko Okumura, Hideoki Ogawa, Shigaku Ikeda
    • Organizer
      日本研究皮膚科学会 第42回年次学術大会・総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Notch signaling contributes to differentiation of mucosal mast cells and development of experimental food allergy2016

    • Author(s)
      Nobuhiro Nakano, Asuka Honjo, Ko Okumura, Hideoki Ogawa, Shigaku Ikeda
    • Organizer
      日本研究皮膚科学会 第41回年次学術大会・総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Inhibition of Notch signaling suppresses food antigen-induced mucosal mast cell hyperplasia2016

    • Author(s)
      NAKANO Nobuhiro, HONJO Asuka, YAMAZAKI Susumu, OHTSUKA Yoshikazu, YAGITA Hideo, SHIMIZU Toshiaki, OKUMURA Ko, OGAWA Hideoki
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県・宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Notchシグナル阻害による食物アレルギーの症状の軽減2016

    • Author(s)
      中野信浩、本庄明日香、西山千春、大塚宜一、清水俊明、奥村 康、小川 秀興
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] TGF-β-induced suppression of mast cell functions is mediated by the transcription factor Ehf2015

    • Author(s)
      Nobuhiro Nakano, Susumu Yamazaki, Chiharu Nishiyama, Ko Okumura, Hideoki Ogawa, Shigaku Ikeda
    • Organizer
      日本研究皮膚科学会 第40回年次学術大会・総会
    • Place of Presentation
      岡山コンベンションセンター(岡山県・岡山市)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Notch signaling enhances mast cell cytokine production through direct and indirect mechanisms2015

    • Author(s)
      Nobuhiro Nakano, Chiharu Nishiyama, Hideo Yagita, Ko Okumura, and Hideoki Ogawa
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Notchシグナルによるマスト細胞のTh2サイトカイン産生増強メカニズムの解析2015

    • Author(s)
      中野信浩、西山千春、八木田秀雄、奥村康、小川秀興
    • Organizer
      第64回日本アレルギー学会学術大会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都・品川区)
    • Year and Date
      2015-05-26
    • Related Report
      2015 Research-status Report
  • [Remarks] 順天堂大学大学院医学研究科アトピー疾患研究センターのホームページ

    • URL

      http://www.juntendo.ac.jp/graduate/laboratory/labo/atopy_center/

    • Related Report
      2017 Annual Research Report 2016 Research-status Report 2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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