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Pathogenic mechanisms of atopic dermatitis

Research Project

Project/Area Number 25253071
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Kawakami Toshiaki  国立研究開発法人理化学研究所, 統合生命医科学研究センター, チームリーダー (60143418)

Co-Investigator(Kenkyū-buntansha) Izuhara Kenji  佐賀大学, 医学部, 教授 (00270463)
Matsumoto Kenji  国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 部長 (60181765)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000)
Fiscal Year 2015: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2014: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2013: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Keywordsアトピー性皮膚炎 / マスト細胞 / Phospholipase C-β3 / Stat5 / Periostin / TSLP
Outline of Final Research Achievements

Atopic dermatitis (AD) is a chronic inflammatory skin disease featured with itching and type 2 inflammation. Evidence has been accumulated showing that skin barrier impairment and immune dysregulation underlie the disease. This research project has been focused on revealing the disease pathogenesis at the cellular and molecular levels by studying murine AD models that develop skin inflammation in either a spontaneous or allergen-induced manner. So far, our data have shown that mast cells, but not basophils, are required for allergen-induced skin inflammation. Our analysis of conditional knockout mice lacking the Plcb3 gene encoding phospholipase C-β3 in various cell-specific fashions has not been completed yet. However, our data indicate that Plcb3 in CD4 T cells is not required for spontaneous development of AD-like skin inflammation in Plcb3-decifient mice.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (29 results)

All 2015 2014 2013 Other

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 10 results) Book (2 results)

  • [Journal Article] Hypothetical atopic dermatitis-myeloproliferative neoplasm syndrome.2015

    • Author(s)
      Kawakami, T., Ando, T., and Kawakami, Y.
    • Journal Title

      Front. Immunol.

      Volume: 6 Pages: 434-434

    • DOI

      10.3389/fimmu.2015.00434

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation.2015

    • Author(s)
      Carroll-Portillo, A., Cannon, J.L., te Riet, J., Holmes, A., Kawakami, Y., Kawakami, T., Cambi, A., and Lidke, D.S.
    • Journal Title

      J. Cell Biol.

      Volume: 210 Issue: 5 Pages: 851-864

    • DOI

      10.1083/jcb.201412074

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Signal transduction and chemotaxis in mast cells.2015

    • Author(s)
      Draber, P., Halova, I., Polakovicova, I., and Kawakami, T.
    • Journal Title

      Eur. J. Pharmacol.

      Volume: 778 Pages: 11-23

    • DOI

      10.1016/j.ejphar.2015.02.057

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Suplatast tosilate for treating cutaneous mastocytosis2015

    • Author(s)
      Yasudo, H., Ando, T., Hiwatari, M., and Oka, A.
    • Journal Title

      Pediatric Dermatology

      Volume: 32 Issue: 3

    • DOI

      10.1111/pde.12552

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal transduction and chemotaxis in mast cells2015

    • Author(s)
      Draber, P., Halova, I., Polakovicova, I., and Kawakami, T.
    • Journal Title

      European Journal of Pharmacology

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アレルギー疾患におけるヒスタミン遊離因子の関与2015

    • Author(s)
      柏倉淳一, 安藤智暁, 川上敏明
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 63 Pages: 84-88

    • NAID

      40020330518

    • Related Report
      2014 Annual Research Report
  • [Journal Article] アトピー性皮膚炎におけるマスト細胞のStat5活性化経路の関与2015

    • Author(s)
      安藤智暁,川上敏明
    • Journal Title

      臨床免疫・アレルギー科

      Volume: in press

    • NAID

      40020505178

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Signal-transducing adaptor protein-2 controls the IgE-mediated, mast cell-mediated anaphylactic responses.2014

    • Author(s)
      Sekine Y, Nishida K, Yamasaki S, Muromoto R, Kon S, Kashiwakura J, Saitoh K, Togi S, Yoshimura A, Oritani K, Matsuda T
    • Journal Title

      J Immunol

      Volume: 192 Issue: 8 Pages: 3488-3495

    • DOI

      10.4049/jimmunol.1300886

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria2014

    • Author(s)
      Fujisawa, D., Kashiwakura, J., Kita, H., Kikukawa, Y., Fujitani, Y., Sasaki-Sakamoto, Y., Kuroda, K., Nunomura, S., Hayama, K., Terui, T., Ra, C., and Okayama, Y.
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 134 Issue: 3 Pages: 622-633

    • DOI

      10.1016/j.jaci.2014.05.004

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Systemic lupus erythematosus complicated with liver cirrhosis in a patient with Papillon-Lefevre syndrome2014

    • Author(s)
      Yasudo, H., Ando, T., Takeuchi, M., Nakano, H., Itonaga, T., Takehara, H., Isojima, T., Miura, K., Harita, Y., Takita, J., and Oka, A.
    • Journal Title

      Lupus

      Volume: 23 Issue: 14 Pages: 1523-1527

    • DOI

      10.1177/0961203314547794

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histamine-releasing factor and immunoglobulins in asthma and allergy2014

    • Author(s)
      Kawakami, T., Kashiwakura, J., and Kawakami, Y.
    • Journal Title

      Allergy, Asthma & Immunology Research

      Volume: 6 Issue: 1 Pages: 6-12

    • DOI

      10.4168/aair.2014.6.1.6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] アレルギー炎症とIgE Heterogeneityヒスタミン遊離因子によるマスト細胞活性化調節2014

    • Author(s)
      柏倉淳一, 安藤智暁, 川上敏明
    • Journal Title

      化学と生物

      Volume: 52 Pages: 496-498

    • NAID

      130005090119

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Immune regulation by phospholipase C-βisoforms.2013

    • Author(s)
      Xiao, W., Kawakami, Y., and Kawakami, T.
    • Journal Title

      Immunol. Res.

      Volume: 56 Issue: 1 Pages: 9-19

    • DOI

      10.1007/s12026-012-8341-3

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mast cells are required for full expression of allergen/SEB-induced skin inflammation.2013

    • Author(s)
      Ando, T., Matsumoto, K., Namiranian, S., Yamashita, H., Glatthorn, H., Kimura, M., Dolan, B. R., Lee, J.J., Galli, S.J., Kawakami, Y., Jamora, C., and Kawakami, T.
    • Journal Title

      J. Invest. Dermatol.

      Volume: 133 Issue: 12 Pages: 2695-2705

    • DOI

      10.1038/jid.2013.250

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Salmonella’s masterful skill in mast cell suppression.2013

    • Author(s)
      Kawakami, T. and Ando, T.
    • Journal Title

      Immunity

      Volume: 39 Issue: 6 Pages: 996-998

    • DOI

      10.1016/j.immuni.2013.11.007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role for mast-cell Stat5 activity in skin inflammation.2013

    • Author(s)
      Ando, T., Xiao, W., Gao, P., Namiranian, S., Matsumoto, K., Tomimori, Y., Hong, H., Yamashita, H., Kimura, M., Kashiwakura, J., Hata, T.R., Izuhara, K., Gurish, M.F., Roers, A., Rafaels, N.M., Barnes, K.C., Jamora, C., Kawakami, Y., and Kawakami, T.
    • Journal Title

      Cell Reports

      Volume: 6 Issue: 2 Pages: 366-376

    • DOI

      10.1016/j.celrep.2013.12.029

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Histamine-releasing factor in food allergy.2015

    • Author(s)
      Kawakami, T.
    • Organizer
      The 7th EMBRN International Mast Cell and Basophil Meeting
    • Place of Presentation
      Marseille, France
    • Year and Date
      2015-10-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Phospholipase C-β3 in the defense against skin inflammation.2015

    • Author(s)
      Kawakami, T.
    • Organizer
      SPC-NUS Workshop “Mast cells in immune disorders and tissue homeostasis
    • Place of Presentation
      Paris, France.
    • Year and Date
      2015-10-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mast cells and the Stat5 activation pathway are required for allergen-induced and spontaneous skin inflammation2014

    • Author(s)
      Tomoaki Ando, Jun-ichi Kashiwakura, Yuko Kawakami, Toshiaki Kawakami
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館、京都市
    • Year and Date
      2014-12-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Critical role for mast-cell Stat5 activity in atopic dermatitis2014

    • Author(s)
      Kawakami, T.
    • Organizer
      Academy of Immunology and Microbiology (AIM) Workshop on Immunology 2014
    • Place of Presentation
      Pohang, Republic of Korea
    • Year and Date
      2014-11-09 – 2014-11-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Atopic dermatitis and hematopoietic malignancy: Lessons from studies on2014

    • Author(s)
      Kawakami, T.
    • Organizer
      The 14th Annual Meeting of The Korean Atopic
    • Place of Presentation
      Seoul, Republic of Korea
    • Year and Date
      2014-11-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Critical role for mast-cell Stat5 activity in atopic dermatitis2014

    • Author(s)
      Kawakami, T.
    • Organizer
      The LJI-USC Immunology Retreat
    • Place of Presentation
      La Jolla, California, USA
    • Year and Date
      2014-04-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Phospholipase C-β3 as a tumor suppressor and a guardian of the immune system

    • Author(s)
      Toshiaki Kawakami
    • Organizer
      Special International Symposium “Inositide-Dependent Phospholipase C Activity and Signalling”
    • Place of Presentation
      Ulsan, South Korea
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Stat5 regulation: a crucial mediator in mast cell-dependent skin inflammation

    • Author(s)
      Toshiaki Kawakami
    • Organizer
      The 7th International Leukocyte Signal Transduction Conference
    • Place of Presentation
      Kos, Greece
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Phospholipase C-β3 as a tumor suppressor and a guardian of the immune system

    • Author(s)
      Toshiaki Kawakami
    • Organizer
      The 5th LIAI-IMS Workshop
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Phospholipase C-β3 as a tumor suppressor and a guardian of the immune system

    • Author(s)
      Toshiaki Kawakami
    • Organizer
      2013 International Conference “Inflammation,Cancer and Metabolic Disorders”
    • Place of Presentation
      Zhunan, Miaoli, Taiwan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Breakfast Seminar entitled “New insights into IgE biology”

    • Author(s)
      Toshiaki Kawakami
    • Organizer
      The Annual Meeting of American Academy of Allergy, Asthma and Immunology
    • Place of Presentation
      San Diego, California, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] A Mouse Model of Atopic Dermatitis. In Mast Cells: Methods and Protocols,Methods in Molecular Biology vol. 1220, (eds. Michael R. Hughes and Kelly M. McNagny)2015

    • Author(s)
      Kawakami, Y. and Kawakami, T
    • Total Pages
      540
    • Publisher
      Springer Science+Business Media
    • Related Report
      2014 Annual Research Report
  • [Book] Basic Techniques to Study FcεRI Signaling in Mast Cells. In Mast Cells: Methods and Protocols, Methods in Molecular Biology vol. 1220, (eds. Michael R. Hughes and Kelly M. McNagny)2014

    • Author(s)
      Kawakami, Y. and Kawakami, T.
    • Total Pages
      540
    • Publisher
      Springer Science+Business Media
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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