The role of the skin innate immunity in inflammatory skin diseases

• Project/Area Number: 24591622
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tohoku University
• Principal Investigator: YAMASAKI Kenshi 東北大学, 医学(系)研究科(研究院), 准教授 (40294798)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: カセリサイディン / ＩＬ－３６ / 表皮角化細胞 / 自然免疫 / サイトカイン / ケモカイン / 皮膚炎症 / 抗菌ペプチド

Outline of Final Research Achievements

in order to how the innate immune system affect skin inflammatory disease, we examined how cathelicidin affect human epidermal keratinocytes and inflammatory cell in this study. We identified IL-36s, IL-1 family molecules, are induced by the cathelicidin peptide stimulation in human keratinocytes. Cathelicidin and IL-36s are additively or synergisticcally induced inflammatory cytokines in human keratinocytes. We also observed that cathelicidin and IL-36s are coordinately expressed in the lesional epidermis of the psoriasis, a chronic skin inflammatory diseases. These suggested that cathelicidin and IL-36s exacerbate human skin diseases such as psoriasis.

Research Products

• [Journal Article] Alarmin Function of Cathelicidin Antimicrobial Peptide LL37 through IL-36gamma Induction in Human Epidermal Keratinocytes (2014)
  • Author(s): Li, N. Yamasaki, K. Saito, R. Fukushi-Takahashi, S. Shimada-Omori, R. Asano, M. Aiba, S.
  • Journal Title: J Immunol Volume: 193 Issue: 10 Pages: 5140-8
  • DOI: 10.4049/jimmunol.1302574
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Antimicrobial peptide LL-37 produced by HSV-2-infected keratinocytes enhances HIV infection of Langerhans cells (2013)
  • Author(s): Ogawa Y, Kawamura T, Matsuzawa T, Aoki R, Gee P, Yamashita A, Moriishi K, Yamasaki K, Koyanagi Y. Blauvelt A, Shimada S.
  • Journal Title: Cell Host and Microbe Volume: 13 Issue: 1 Pages: 77-86
  • DOI: 10.1016/j.chom.2012.12.002
  • Peer Reviewed
• [Journal Article] In vivo imaging demonstrates ATP release from murine keratinocytes and its involvement in cutaneous inflammation after tape-stripping (2013)
  • Author(s): Takahashi, T., Kimura, Y., Niwa, K., Ohmiya, Y., Fujimura, T., Yamasaki, K., and Aiba, S.
  • Journal Title: J Invest Dermatol Volume: 133 Issue: 10 Pages: 2407-15
  • DOI: 10.1038/jid.2013.163
  • Peer Reviewed
• [Journal Article] Activation of epidermal toll-like receptor 2 enhances tight junction function : implications for atopic dermatitis and skin barrier repair (2013)
  • Author(s): Kuo, I. H., Carpenter-Mendini, A., Yoshida, T., McGirt, L. Y., Ivanov, A. I., Barnes, K. C., Gallo, R. L., Borkowski, A. W., Yamasaki, K., Leung, D. Y., Georas, S. N., De Benedetto, A., and Beck, L. A.
  • Journal Title: J Invest Dermatol Volume: 133 Issue: 4 Pages: 988-998
  • DOI: 10.1038/jid.2012.437
  • Peer Reviewed
• [Journal Article] Cathelicidin antimicrobial peptide LL-37 in psoriasis enables keratinocyte reactivity against TLR9 ligands (2012)
  • Author(s): Morizane, S., Yamasaki, K., Muhleisen, B., Kotol, P. F., Murakami, M., Aoyama, Y., Iwatsuki, K., Hata, T., and Gallo, R. L.
  • Journal Title: J Invest Dermatol Volume: 132 Issue: 1 Pages: 135-143
  • DOI: 10.1038/jid.2011.259
  • Peer Reviewed
• [Journal Article] TH2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis (2012)
  • Author(s): Morizane, S., Yamasaki, K., Kajita, A., Ikeda, K., Zhan, M., Aoyama, Y., Gallo, R. L., and Iwatsuki, K.
  • Journal Title: J Allergy Clin Immunol Volume: 130 Issue: 1 Pages: 259-261
  • DOI: 10.1016/j.jaci.2012.03.006
  • NAID: 130004505789
  • Peer Reviewed
• [Presentation] Alarmin function of Cathelicidin antimicrobial peptide LL37 through IL-36s induction and p38 MAPK pathway in keratinocytes. (2013)
  • Author(s): 李娜、山崎研志
  • Organizer: 国際研究皮膚科学会
  • Place of Presentation: エジンバラ、英国