The role of Th17 cells in the pathogenesis of autoimmune blistering disease

• Project/Area Number: 16K10141
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: Iwata Hiroaki 北海道大学, 大学病院, 助教 (20397334)
• Co-Investigator(Kenkyū-buntansha): 西江 渉 北海道大学, 医学研究院, 准教授 (20443955) ; 氏家 英之 北海道大学, 大学病院, 講師 (60374435)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自己免疫性水疱症 / 尋常性乾癬 / 経皮免疫 / Th17細胞 / 自己免疫 / Th17 / 後天性表皮水疱症 / 7型コラーゲン / 水疱症

Outline of Final Research Achievements

We tried the establishment of the autoimmune blistering disease mouse model induced by epicutaneous immunization instead of subctaneous injection. In this process, imiquimod cream was applied onto the mouse back skin, and then antigen protein was applied on the inflamed skin. Imiquimod cream is known to activate dendritic cell in the skin and induce Th17 cells. Compared to conventional subctaneous immunization with adjuvant, epicutaneous immunization induced the autoaintibodies less frequently and also less titier levels. However, epicutaneous immunization without adjuvant could induce autoantibodies in several mice.

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患は皮膚疾患の一つ尋常性乾癬に高率に合併するすることが知られているが、その理由は明らかではない。我々の結果は、尋常性乾癬の病態（Th17細胞優位）が、自己免疫性水疱症をきたしやすい可能性を示唆する所見である。つまり、ある種の皮膚疾患をきちんと治療コントロールできないと、さらなる次の疾患が生じてくる可能性を示している。合併症を増やさないためにも、病気を適切に治療することの必要性を示す重要な結果である。

Research Products

• [Journal Article] Fc-binding proteins enhance autoantibody-induced BP180 depletion in pemphigoid (2019)
  • Author(s): Iwata H, Kamaguchi M, Ujiie H, Ujiie I, Natsuga K, Nishie W, ShimizuH:
  • Journal Title: J Pathol Volume: 247 Issue: 3 Pages: 371-380
  • DOI: 10.1002/path.5196
  • Peer Reviewed
• [Journal Article] The direct binding of collagen XVII and collagen IV is disrupted by pemphigoid autoantibodies (2018)
  • Author(s): Kamaguchi Mayumi、Iwata Hiroaki、Nishie Wataru、Toyonaga Ellen、Ujiie Hideyuki、Natsuga Ken、Kitagawa Yoshimasa、Shimizu Hiroshi
  • Journal Title: Laboratory Investigation Volume: 99 Issue: 1 Pages: 48-57
  • DOI: 10.1038/s41374-018-0113-9
  • Peer Reviewed
• [Journal Article] Oral mucosa is a useful substrate for detecting autoantibodies of mucous membrane pemphigoid. (2018)
  • Author(s): Kamaguchi M, Iwata H, Ujiie H, Izumi K, Natsuga K, Nishie W, Asaka T, Kitagawa Y, Shimizu H.
  • Journal Title: Br J Dermatol. Volume: 178 Issue: 2 Pages: e119-e121
  • DOI: 10.1111/bjd.15925
  • Peer Reviewed
• [Journal Article] High Expression of Collagen XVII Compensates for Its Depletion Induced by Pemphigoid IgG in the Oral Mucosa. (2018)
  • Author(s): Kamaguchi M, Iwata H, Ujiie H, Natsuga K, Nishie W, Kitagawa Y, Shimizu H.
  • Journal Title: J Invest Dermatol. Volume: - Issue: 8 Pages: 1707-1715
  • DOI: 10.1016/j.jid.2018.03.002
  • Peer Reviewed