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A molecular mechanism of atopic manifestations of hyper-IgE syndrome

Research Project

Project/Area Number 25293232
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Pediatrics
Research InstitutionThe University of Tokushima

Principal Investigator

MINEGISHI Yoshiyuki  徳島大学, 疾患プロテオゲノム研究センター, 教授 (10343154)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords原発性免疫不全症 / アトピー性皮膚炎 / STAT3 / 高IgE症候群 / 免疫不全症 / アレルギー / 免疫学
Outline of Final Research Achievements

We identified that hyper-IgE syndrome is caused by dominant negative mutations of the STAT3 gene. Almost all the patients with hyper-IgE syndrome suffer from atopic dermatitis, but a molecular mechanism of the skin manifestation remain unidentified and no treatment other than palliative treatment is available. To address this issue, we establish a model mouse of hyper-IgE syndrome. We evaluated several skin-inflammation models and found that repetitive oxazolone application to the skin is the most useful model for atopic dermatitis by evaluating itching behavior, thickening of epidermis, recruitment of CD4+T cells and eosinophils, increased oxazolone-specific IgE antibody and Th2 cytokines.

Report

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

    (30 results)

All 2016 2015 2014 2013 Other

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome.2015

    • Author(s)
      Kreins A.Y, Ciancanelli M.J, Boisson-Dupuis S, et al.
    • Journal Title

      J Exp Med.

      Volume: 212 Issue: 10 Pages: 1641-1662

    • DOI

      10.1084/jem.20140280

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies.2015

    • Author(s)
      Ma CS, Wong N, Tangye SG, et al.
    • Journal Title

      J Allergy Clin Immunol

      Volume: 136 Issue: 4 Pages: 993-1006

    • DOI

      10.1016/j.jaci.2015.05.036

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 高IgE症候群2015

    • Author(s)
      峯岸克行
    • Journal Title

      臨床免疫アレルギー科

      Volume: 63 Pages: 251-253

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Journal Article] AD-HIES (Job’s症候群)2015

    • Author(s)
      峯岸克行
    • Journal Title

      日本臨床 免疫症候群III

      Volume: 34 Pages: 235-237

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Comel-Netherton症候群2015

    • Author(s)
      峯岸克行
    • Journal Title

      日本臨床 免疫症候群III

      Volume: 34 Pages: 238-239

    • Related Report
      2015 Annual Research Report
  • [Journal Article] PGM3欠損症2015

    • Author(s)
      峯岸克行
    • Journal Title

      日本臨床 免疫症候群III

      Volume: 34 Pages: 240-241

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 高IgE症候群(Job症候群)2015

    • Author(s)
      峯岸克行
    • Journal Title

      小児科診療

      Volume: 79 Pages: 352-352

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 原発性免疫不全症の原因遺伝子探索の新展開2015

    • Author(s)
      峯岸克行
    • Journal Title

      医学のあゆみ 第1土曜特集

      Volume: 252 Pages: 5-9

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program2014

    • Author(s)
      Nishikawa, Y., Nishijima, H., Matsumoto, M., Morimoto, J., Hirota, F., Takahashi, S., Luche, H., Fehling, H.J., Mouri, Y., Matsumoto, M.
    • Journal Title

      J. Immunol

      Volume: 192 Issue: 6 Pages: 2585-2592

    • DOI

      10.4049/jimmunol.1302786

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simple diagnosis of STAT1 gain-of-function alleles in patients with chronic mucocutaneous candidiasis.2014

    • Author(s)
      Mizoguchi Y, Tsumura M, Okada S, Hirata O, Minegishi S, Imai K, Hyakuna N, Muramatsu H, Kojima S, Ozaki Y, Imai T, Takeda S, Okazaki T, Ito T, Yasunaga S, Takihara Y, Bryant VL, Kong XF, Cypowyj S, Boisson-Dupuis S, Puel A, Casanova JL, Morio T, Kobayashi M.
    • Journal Title

      J. Leukoc. Biol.

      Volume: 95 Issue: 4 Pages: 667-76

    • DOI

      10.1189/jlb.0513250

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 高IgE症候群の病態形成メカニズム2014

    • Author(s)
      峯岸克行
    • Journal Title

      炎症と免疫

      Volume: 22 Pages: 18-22

    • Related Report
      2014 Annual Research Report
  • [Journal Article] arasuyama H. Inflammatory monocytes recruited to allergen-exposed skin acquire an anti-inflammatory property via basophil-derived IL-4.2013

    • Author(s)
      Egawa M, Mukai K, Yoshikawa S, Iki M, Kawano Y, Minegishi Y
    • Journal Title

      Immunity

      Volume: 38 Issue: 3 Pages: 570-580

    • DOI

      10.1016/j.immuni.2012.11.014

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The skin is an important bulwark of acquired immunity against intestinal helminths2013

    • Author(s)
      Obata-Ninomiya, K., Ishiwata, K., Tsutsui, H., Nei, Y., Yoshikawa, S., Kawano, Y., Minegishi, Y., Ohta, N., Watanabe, N., Kanuka, H., and Karasuyama, H.
    • Journal Title

      J. Exp. Med.

      Volume: 210 Issue: 12 Pages: 2583-2595

    • DOI

      10.1084/jem.20130761

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] STAT3の異常によるアトピー性皮膚炎の発症機序2013

    • Author(s)
      峯岸克行
    • Journal Title

      臨床・免疫アレルギー科

      Volume: 59 Pages: 160-164

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Jak-Statシグナルとアレルギー制御2013

    • Author(s)
      峯岸克行
    • Journal Title

      実験医学

      Volume: 31 Pages: 113-117

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 高IgE症候群2013

    • Author(s)
      峯岸克行
    • Journal Title

      小児内科

      Volume: 45 Pages: 1146-1147

    • Related Report
      2013 Annual Research Report
  • [Presentation] Molecular pathogenesis of hyper-IgE syndrome2016

    • Author(s)
      Minegishi Y
    • Organizer
      The 5th Bizan Immunology Symposium
    • Place of Presentation
      Tokushima University (徳島県・徳島市)
    • Year and Date
      2016-03-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dysregulationof T cell dependent antibody response in a murine model of hyper IgE syndrome2015

    • Author(s)
      Nishikawa Y, Wada T, Minegishi Y
    • Organizer
      The 44th annual meeting of the Japanese society for Immunology
    • Place of Presentation
      Sapporo Convention Center (北海道・札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hyper-IgE syndrome model mice exhibit the susceptibility to Staphyloccocus aureus infection2015

    • Author(s)
      Wada T, Nishikawa Y, Minegishi Y
    • Organizer
      The 44th annual meeting of the Japanese society for Immunology
    • Place of Presentation
      Sapporo Convention Center (北海道・札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular mechanisms and therapeutic approaches of hyper-IgE syndrome2015

    • Author(s)
      Yoshiyuki Minegishi
    • Organizer
      The 4th Bizan Immunology symposium
    • Place of Presentation
      徳島大学(徳島県徳島市)
    • Year and Date
      2015-01-29 – 2015-01-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Specific DSB induction to STAT3 mutations by CRISPR/Cas92015

    • Author(s)
      Minegishi S, Urabe K, F Inoue, Y Minegishi
    • Organizer
      Keystone symposium “Precision Genome Engineering and Synthetic Biology
    • Place of Presentation
      Big Sky, MN, USA
    • Year and Date
      2015-01-11 – 2015-01-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト遺伝性アレルギー疾患「高IgE症候群」の発症機構の解明とその制御2014

    • Author(s)
      峯岸克行
    • Organizer
      第3回CREST免疫機構領域シンポジウム
    • Place of Presentation
      東京医科歯科大学大講堂(東京都文京区)
    • Year and Date
      2014-10-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 高IgE症候群の病因と病態の解明2014

    • Author(s)
      峯岸克行
    • Organizer
      第21回日本免疫毒性学会学術年会
    • Place of Presentation
      徳島文理大学・国際会議場(徳島県徳島市)
    • Year and Date
      2014-09-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] A Molecular Mechanism of Hyper IgE Syndrome2014

    • Author(s)
      Minegishi Y
    • Organizer
      The third Bizan Immunology Symposium
    • Place of Presentation
      藤井節郎記念ホール(徳島県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] A molecular mechanism underlysing atopic dermatitis in hyper-IgE syndrome2014

    • Author(s)
      Saito M, Karasuyama H, Minegishi Y
    • Organizer
      American Academy of Allergy Asthma Immunology
    • Place of Presentation
      Convention center (San Diego, USA)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アレルギーを合併する免疫不全症 高IgE症候群の病因と病態2013

    • Author(s)
      峯岸克行
    • Organizer
      第116回日本小児科学会学術集会
    • Place of Presentation
      広島国際会議場(広島県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] アトピー性皮膚炎を合併する免疫難病の病態解明2013

    • Author(s)
      峯岸克行
    • Organizer
      第43回日本皮膚アレルギー・接触皮膚炎学会
    • Place of Presentation
      ホテル日航金沢(石川県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] A Molecular Mechanism of Hyper IgE Syndrome2013

    • Author(s)
      Minegishi Y
    • Organizer
      The 4th Japanese Society of Hematology “Dysfunction and Neoplasia of lymphocytes
    • Place of Presentation
      大和屋本店(愛媛県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] 内科学 第10版2013

    • Author(s)
      峯岸克行
    • Total Pages
      2404
    • Publisher
      朝倉書店
    • Related Report
      2013 Annual Research Report
  • [Remarks] 徳島大学疾患プロテオゲノム研究センター

    • URL

      http://www.genome.tokushima-u.ac.jp/

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2019-07-29  

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