Contribution of mast cell functions to the pathogenesis of allergic inflammatory diseases and role of Notch signaling in regulating mast cell functions

• Project/Area Number: 24591667
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Juntendo 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): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アレルギー / マスト細胞 / Notchシグナル / サイトカイン / Notch

Outline of Final Research Achievements

Cytokines produced by mast cells play an important role in the pathogenesis and exacerbation of allergic inflammatory diseases. This study revealed that signaling through cell surface Notch receptors enhances the production of Th2 and inflammatory cytokines by mast cells through direct and indirect mechanisms. Furthermore, results from this study suggest that Notch signaling contributes to the maturation of mucosal-type mast cells, and thus I have analyzed the molecular mechanisms of Notch-induced mast cell maturation.

Research Products

• [Journal Article] Notch signaling enhances FceRI-mediated cytokine production by mast cells through direct and indirect mechanisms (2015)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Critical Roles for PU.1, GATA1, and GATA2 in the Expression of Human FcεRI on Mast Cells: PU.1 and GATA1 Transactivate FCER1A, and GATA2 Transactivates FCER1A and MS4A2 (2014)
  • Author(s): Inage E, Kasakura K, Yashiro T, Suzuki R, Baba Y, Nakano N, Hara M, Tanabe A, Oboki K, Matsumoto K, Saito H, Niyonsaba F, Ohtsuka Y, Ogawa H, Okumura K, Shimizu T, and Nishiyama C
  • Journal Title: Journal of Immunology Volume: 192 Issue: 8 Pages: 3936-46
  • DOI: 10.4049/jimmunol.1302366
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Circadian regulation of allergic reactions by the mast cell clock in mice. (2014)
  • Author(s): Nakamura Y, Nakano N, Ishimaru K, Hara M, Ikegami T, Tahara Y, Katoh R, Ogawa H, Okumura K, Shibata S, Nishiyama C, Nakao A
  • Journal Title: J Allergy Clin Immunol Volume: 133(2) Issue: 2 Pages: 568-575
  • DOI: 10.1016/j.jaci.2013.07.040
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. (2012)
  • Author(s): Hirota T
  • Journal Title: Nat Genet Volume: 44 Issue: 11 Pages: 1222-6
  • DOI: 10.1038/ng.2438
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 inhibition restores ultraviolet B-induced downregulation of ATP2A2/SERCA2 in keratinocytes : possible therapeutic approach of cyclooxygenase-2 inhibition for treatment of Darier disease (2012)
  • Author(s): Kamijo, M., C. Nishiyama, A. Takagi, N. Nakano, M. Hara, S. Ikeda, K. Okumura, and H. Ogawa
  • Journal Title: Br J Dermatol Volume: 166 Issue: 5 Pages: 1017-1022
  • DOI: 10.1111/j.1365-2133.2011.10789.x
  • Peer Reviewed
• [Journal Article] Role of PU.1 in MHC class II expression through transcriptional regulation of class II transactivator pI in dendritic cells (2011)
  • Author(s): Kitamura N., et al
  • Journal Title: J Allergy Clin Immunol Volume: (未定)(in press) Issue: 3 Pages: 814-824
  • DOI: 10.1016/j.jaci.2011.10.019
  • Peer Reviewed
• [Presentation] TGF-βによるマスト細胞機能の抑制を仲介する転写因子Ehfの機能解析 (2015)
  • Author(s): 中野信浩、山﨑晋、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 2015年度大会
  • Place of Presentation: 岡山大学津島キャンパス（岡山県・岡山市）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] Maturation of mucosal mast cells is promoted by Notch signaling (2014)
  • Author(s): Nobuhiro Nakano, Chiharu Nishiyama, Ko Okumura, Shigaku Ikeda, Hideoki Ogawa
  • Organizer: 日本研究皮膚科学会 第39回年次学術大会・総会
  • Place of Presentation: ホテル阪急エキスポパーク（大阪府・吹田市）
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] 粘膜型マスト細胞分化におけるNotchシグナルとIL-3シグナルの協調作用 (2014)
  • 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2014年度大会
  • Place of Presentation: 明治大学生田キャンパス、神奈川県川崎市
• [Presentation] NotchシグナルはIL-3存在下において粘膜型マスト細胞の分化を促進する (2013)
  • Author(s): 中野信浩、西山千春、奥村康、小川秀興
  • Organizer: 第63回日本アレルギー学会秋季学術大会
  • Place of Presentation: ホテルニューオータニ、東京
• [Presentation] Notch1 signaling confers antigen-presenting functions on mast cells (2013)
  • Author(s): Nobuhiro Nakano, Chiharu Nishiyama, Hideo Yagita, Ko Okumura, Hideoki Ogawa
  • Organizer: 15th International Congress of Immunology - ICI 2013
  • Place of Presentation: Milano Congressi, Milan, Italy
• [Presentation] 粘膜型マスト細胞の分化・成熟におけるNotchシグナルの役割
  • Author(s): 中野信浩
  • Organizer: 日本農芸化学会 2013年度大会
  • Place of Presentation: 東北大学 川内北キャンパス（仙台）
• [Presentation] Notch signaling augments mast cell cytokine production by direct and indirect mechanisms
  • Author(s): 中野信浩
  • Organizer: 日本研究皮膚科学会 第37回年次学術大会・総会
  • Place of Presentation: パシフィックホテル沖縄（那覇）
• [Presentation] Notchシグナルによって成熟が誘導された粘膜型マスト細胞の形質と機能
  • Author(s): 中野信浩
  • 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（大阪）
• [Remarks] 順天堂大学アトピー疾患研究センターホームページ
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/atopy_center/
• [Remarks] 順天堂大学アトピー疾患研究センターホームページ
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/atopy_center/
• [Remarks] アトピー疾患研究センター
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/atopy_center/index.html