Involvement of microflora-induced Th17 cells in psoriasis

• Project/Area Number: 22659207
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Ehime University
• Principal Investigator: SAYAMA Koji 愛媛大学, 大学院・医学系研究科, 教授 (80187286)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,230,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 無菌マウス / SPF / 自然免疫 / Th17 / 黄色ブドウ球菌 / 表皮ブドウ球菌 / TLR / 細菌感染 / 尋常性乾癬 / 角化細胞 / インフラマソーム / 細菌 / 表皮分化

Research Abstract

Skin phenotypes of germ-free mice were compared with those of control SPF mice. The epidermis of germ-free mice was atrophic compared to SPF mice. Markers for keratinocyte differentiation such as keratins were histologically stained. Next, we studied whether pathogens can be a trigger for the development of psoriasis. S. aureus and S. epidermidis were heat-inactivated and added to the cultured keratinocytes. Cytokines and anti-microbial peptides were induced. Imiquimod, an activator of innate immunity, was used for the development of psoriatic skin lesions. Back skin of the mice was shaved and imiquimod was topically applied for the five consecutive days. One week after the application, erythema and scales appeared on the skin. Histological analyses confirmed the development of psoriasis.

Research Products

• [Journal Article] Mite allergen is a danger signal for the skin via activation of the inflammasome in keratinocytes (2011)
  • Author(s): Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S, Yang L, Hirakawa S, and Hashimoto K.
  • Journal Title: J Allergy Clin Immunol Volume: 127 Pages: 806-814
  • Peer Reviewed
• [Journal Article] Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation (2011)
  • Author(s): Okazaki H, Tokumaru S, Hanakawa Y, Shiraishi K, Shirakata Y, Dai X, Yang L, Tohyama M, Hashimoto K, and Sayama K.
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Pages: 441-445
  • Peer Reviewed
• [Journal Article] Inflammatory mediator TAK1 regulates hair follicle morphogenesis and anagen induction shown by using keratinocyte-specific TAK1-dificient mice. (2010)
  • Author(s): Sayama K, Kajiya K, Sugawara K, Sato S, Hirakawa S, Shirakata Y, Hanakawa Y, Dai X, Ishimatsu-Tsuji Y, Metzger D, Chambon P, Akira S, Paus R, Kishimoto J, and Hashimoto K.
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Journal Article] E2 polyubiquitin-conjugating enzyme Ubc 13 in keratinocytes is essential for epidermal integrity (2010)
  • Author(s): Sayama K, Yamamoto M, Shirakata Y, Hanakawa Y, Hirakawa S, Dai X, Tohyama M, Tokumaru S, Shin MS, Sakurai H, Akira S, and Hashimoto K.
  • Journal Title: J Biol Chem Volume: 285 Pages: 30042-30049
  • Peer Reviewed
• [Journal Article] PPARγmediates innate immunity by regulating the 1α, 25-dihydroxyvitamin D3 induced hBD-3 and cathelicidin in human keratinocytes (2010)
  • Author(s): Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S, Yang L, Hirakawa S, and Hashimoto K.
  • Journal Title: J Dermatol Sci Volume: 60 Pages: 179-186
  • Peer Reviewed
• [Journal Article] E2 polyubiquitin-conjugating enzyme Ubc13 in keratinocytes is essential for epidermal integrity. (2010)
  • Author(s): Sayama K
  • Journal Title: J Biol Chem Volume: 285 Pages: 30042-9
  • Peer Reviewed
• [Journal Article] PPAR-γ mediates innate immunity by regulating the 1α, 25-dihydroxyvitamin D3 induced hBD-3 and cathelicidin in human keratinocytes (2010)
  • Author(s): Dai X, et al.
  • Journal Title: J Dermatol Sci Volume: 60 Pages: 179-86
  • Peer Reviewed
• [Journal Article] Inflammatory mediator TAK1 regulates hair follicle morphogenesis and anagen induction shown by using keratinocyte-specific TAK1-deficient mice. (2010)
  • Author(s): Sayama K
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Presentation] Mite allergen activates inflammasome in epidermal keratinocytes resulting in the production of IL-1beta and IL-18 (2011)
  • Author(s): Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S, Yang L, Hirakawa S, and Hashimoto K.
  • Organizer: 22^<nd> World Congress of Dermatology
  • Place of Presentation: Seoul, Korea
• [Presentation] Mite allergen is a danger signal for the skin (2010)
  • Author(s): Sayama K
  • Organizer: European Society for Investigative Dermatology
  • Place of Presentation: ヘルシンキ/フィンランド
  • Year and Date: 2010-09-10
• [Presentation] Mite allergen is a danger signal for the skin (2010)
  • Author(s): Sayama K, Dai X, Shirakata Y, Tohyama M, Miyawaki S, Hirakawa S, and Hashimoto K.
  • Organizer: 40^<th> Annual ESDR Meeting of the European Society for Dermatological Research
  • Place of Presentation: Helsinki, Finland