The blistering mechanisms in bullous pemphigoid

• Project/Area Number: 26860861
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: Iwata Hiroaki 北海道大学, 大学病院, 特任助教 (20397334)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 自己免疫 / 自己抗原 / 水疱性類天疱瘡 / 17型コラーゲン / 自己免疫疾患 / 自己抗体 / エンドサイトーシス / 自己免疫性疾患 / Trim21 / ユビキチン

Outline of Final Research Achievements

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease associated with autoantibodies to type XVII collagen (COL17). When keratinocytes are treated with BP-IgG, COL17 internalizes into cells by way of the macropinocytosis pathway. The inhibition of small GTPase family members Rac1 and Cdc42 was found to strongly repress COL17 internalization; additionally the Rho inhibitor also partially blocked the internalization.This depletion of COL17 from lateral-apical plasma membrane generates a significant shortage of COL17-supplementation to hemidesmosome, resulting in the formation of incomplete hemidesmsome lacking COL17.

Research Products

• [Presentation] Autoantibodies to parts of type XVII collagen outside of the non-collageneous 16A domain lead to mild bullous pemphigoid due to the non-depletion of autoantigen (2015)
  • Author(s): 1.Iwata H, Imafuku K, Izumi K, Wada M, Natsuga K, Ujiie H, Nishie W, Shimizu H
  • Organizer: The 45th annual meeting of the European Society for Dermatological Research
  • Place of Presentation: Postillion Convention Centre-WTC(Rotterdam, The Netherland)
  • Year and Date: 2015-09-09
  • Int'l Joint Research
• [Presentation] 抗NC16A抗体を有さない軽症の水疱性類天疱瘡の1例 (2015)
  • Author(s): 今福 恵輔、岩田 浩明、泉 健太郎、夏賀 健、氏家 英之、西江 渉、清水 宏
  • Organizer: 第114回日本皮膚科学会総会
  • Place of Presentation: パシフィコ横浜 横浜
  • Year and Date: 2015-05-29 – 2015-05-31