The role of antigen-specific regulatory B cells in imiquimod-induced psoriasis model mice

• Project/Area Number: 17K16325
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: Yoshizaki Asako 東京大学, 医学部附属病院, 助教 (00530411)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 乾癬 / B細胞 / 制御性B細胞 / 皮膚科学 / 炎症学 / 皮膚免疫

Outline of Final Research Achievements

Psoriasis is a chronic inflammatory skin disease that presents with rashes in the background of systemic inflammation. Not only rashes but also arthritis and uveitis are associated at a high rate, it is suggested that the pathogenesis of psoriasis is involved in autoimmunity. B cells have been thought to be involved in autoimmunity by producing autoantibodies. In addition, recently studies have shown that they have various other functions and play a central role in autoimmunity. Many researchers have shown that some B cell populations control the inflammatory response by producing interleukin-10. The present study suggested that regulatory B cells also suppress the pathogenesis of psoriasis.

Academic Significance and Societal Importance of the Research Achievements

乾癬において、制御性B細胞と抗原特異性を検討した研究はこれまで報告が全くなく、極めて独創性の高い研究といえる。抗原特異的制御性B細胞は抗原特異的に作用することで、免疫抑制作用を強める。制御性B細胞を用いたイミキモド乾癬モデルに対する養子移入実験は、乾癬における病態が抗原特異的な免疫反応によって制御されているかを明確化し、新規治療ターゲットの探索を目指す点も独創性を高めている。さらには乾癬において、難治化の原因として制御性B細胞の機能不全が存在する可能性を考える場合においても本研究は重要である。

Research Products

• [Journal Article] Leprosy with spontaneous type 1 lepra reaction as an initial cutaneous manifestation: a case from Japan. (2018)
  • Author(s): Noda M, Tsunemi Y, Masui Y, Yoshizaki A, Ohmatsu H, Takazawa Y, Ishii N.
  • Journal Title: Eur J Dermatol Volume: 28 Pages: 843-844
  • Peer Reviewed
• [Journal Article] Rapid alteration of serum interleukin-6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis-associated interstitial lung disease. (2018)
  • Author(s): Numajiri H, Yoshizaki A, Fukasawa T, Ebata S, Nakamura K, Yamashita T, Saigusa R, Miura S, Hirabayashi M, Yoshizaki A, Sumida H, Asano Y, Kazoe Y, Mawatari K, Kitamori T, Sato S.
  • Journal Title: J Dermatol. Volume: 45 Issue: 10 Pages: 1221-1224
  • DOI: 10.1111/1346-8138.14580
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Single cell analysis revealed that responses to therapy is regulated by B cells in systemic sclerosis-associated interstitial lung disease (2017)
  • Author(s): Satoshi Ebata, Ayumi Yoshizaki, Takemichi Fukasawa, Kouki Nakamura, Takashi Yamashita, Shunsuke Miura, Ryosuke Saigusa, Megumi Hirabayashi, Asako Yoshizaki, Kaname Akamata, Yoshihide Asano, Yutaka Kazoe, Kazuma Mawatari, Takehiko Kitamori, Shinichi Sato
  • Organizer: The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology
  • Int'l Joint Research