Comprehensive analysis of a molecular mechanism of hyper IgE-emia

• Project/Area Number: 25670478
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: The 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 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 高IgE血症 / アトピー性皮膚炎 / 免疫学

Research Abstract

Hyper IgE syndrome is a complex primary immunodeficiency characterized by atopic dermatitis associated with extremely high serum IgE levels and susceptibility to staphylococcal skin abscesses and pneumonia. Our recent studies have demonstrated that dominant negative mutations in the signal transducer and activator of transcription 3 (STAT3) gene result in the hyper IgE syndrome.
Although defective differentiation of Th17 cells may partly accounts for the susceptibility to staphylococcal skin abscesses and pneumonia, the pathogenesis of atopic manifestations in hyper IgE-emia remains to be elucidated. To investigate molecular pathogenesis of hyper IgE syndrome, we established knock-in model mice expressing dominant negative STAT3. In the mice, serum IgE levels were at least 100 times higher than littermate wild-type control mice. With these new model mice in our hand, we will investigate a molecular pathogenesis of hyper IgE-emia in hyper IgE syndrome.

Research Products

• [Journal Article] 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, Karasuyama H
  • Journal Title: Immunity Volume: 38 Pages: 570-580
• [Journal Article] The skin is an important bulwark of acquired immunity against intestinal helminthes (2013)
  • Author(s): Obata-Ninomiya K, Ishiwata K, Tsutsui H, Nei Y, Yoshikawa S, Kawano Y, Minegishi Y, Ohta N, Watanabe N, Kanuka H, Karasuyama H
  • Journal Title: J Exp Med Volume: 210 Pages: 2583-2595
• [Journal Article] Boisson-Dupuis S, Pue1 A, Casanova JL, Morio T, Kobayashi M. Simple diagnosis of STAT1 gain-of-function alleles in patients with chronic mucocutaneous candidiasis (2013)
  • 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
  • Journal Title: J Leukoc Biol Volume: (in press)
• [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
• [Journal Article] 高IgE症候群の最近の話題 (2013)
  • Author(s): 峯岸克行
  • Journal Title: Medical Science Digest Volume: 39 Pages: 7-8
  • NAID: 10026352596
• [Journal Article] 抗体産生不全症-B細胞不全症 (2013)
  • Author(s): 峯岸克行
  • Journal Title: 小児科診療 Volume: 76 Pages: 419-423
• [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
• [Journal Article] 高IgE 症候群に見られる易感染性 (2013)
  • Author(s): 峯岸克行
  • Journal Title: 化学療法の領域 Volume: 29 Pages: 2429-2434
• [Journal Article] 小児内科 (2013)
  • Author(s): 峯岸克行
  • Journal Title: 高IgE症候群 Volume: 45 Pages: 1146-1147
• [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
  • Peer Reviewed
• [Journal Article] The skin is an important bulwark of acquired immunity against intestinal helminths (2013)
  • 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
  • Peer Reviewed
• [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
• [Presentation] A molecular mechanism underlysing atopic dermatitis in hyper-IgE syndrome (2014)
  • Author(s): Saito M, Karasuyama H, Minegishi Y
  • Organizer: American Association of Allergy and Immunology
  • Place of Presentation: Convention Center (San Diego USA)
• [Presentation] Molecular pathogenesis of hyper IgE syndrome (2014)
  • 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）
  • Invited
• [Presentation] A molecular mechanism underlysing atopic dermatitis in hyper-IgE syndrome (2014)
  • Author(s): Saito M, Karasuyama H, Minegishi Y
  • Organizer: American Academy of Allergy Asthma Immunology
  • Place of Presentation: Convention center (San Diego, USA)
• [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)
  • Year and Date: 2013-12-01
• [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) シンポジウム Primary immunodeficiency 2013 update; Current topics and new concepts
  • Year and Date: 2013-04-21
• [Presentation] 高IgE 症候群の診断と治療に関する最近の進歩 (2013)
  • Author(s): 峯岸克行
  • Organizer: 第3回東北小児感染症免疫研究会
  • Place of Presentation: ホテル日航仙台(宮城県)
  • Year and Date: 2013-02-16
• [Presentation] A Molecular Mechanism of Hyper IgE Syndrome (2013)
  • Author(s): Minegishi Y
  • Organizer: The 4th Japanese Society of Hematology "Dysfunction and Neoplasia of lymphocytes"
  • Place of Presentation: Yamatoya Honten, Ehime
• [Presentation] A Molecular Mechanism of Hyper IgE Syndrome (2013)
  • Author(s): Minegishi Y
  • Organizer: The 2nd symposium of the University of Tokushima "Immune system development, deviation, and regulation"
  • Place of Presentation: Nichia Medical Hall, Tokushima University, Tokushima
• [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）
  • 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）
  • Invited
• [Presentation] A Molecular Mechanism of Hyper IgE Syndrome (2013)
  • Author(s): Minegishi Y
  • Organizer: The 4th Japanese Society of Hematology “Dysfunction and Neoplasia of lymphocytes
  • Place of Presentation: 大和屋本館（愛媛県）
  • Invited
• [Book] 内科学 第１０版 (2013)
  • Author(s): 峯岸克行
  • Total Pages: 2404
  • Publisher: 朝倉書店
• [Book] 内科学 第10版 原発性免疫不全症 (1371-1378)総編集 矢崎義男
  • Author(s): 峯岸克行
  • Total Pages: 2404
  • Publisher: 朝倉書店
• [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/