The role of S100A8 and S100A9 in the pathogenesis of atopic dermatitis

• Project/Area Number: 26860326
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kyoto University
• Principal Investigator: Nakajima Saeko 京都大学, 医学(系)研究科(研究院), 研究員 (70574408)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アトピー性皮膚炎 / S100A8 / S100A9

Outline of Final Research Achievements

We aimed to generate keratinocyte specific S100A8 and S100A9 transgenic mice to understand the roles of these S100 proteins in the pathogenesis of atopic dermatitis (AD).
We have generated epidermal keratinocyte specific S100A8 and S100A9 transgenic mice. We are able to induce over expression of S100 proteins with primary cultured-keratinocytes of these mice by adding tetracycline in vitro. Skin dendritic cells and murine bone marrow derived dendritic cells (BMDCs) are highly expressed functional receptors of these S100 proteins. Recombinant S100 proteins are able to induce inflammatory cytokine productions from BMDCs in vitro.
We will apply murine AD model to keratinocyte specific S100A8 and S100A9 transgenic mice and try to understand the roles of S100A8 and S100A9 in the development of AD.

Research Products

• [Journal Article] Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses. (2015)
  • Author(s): Sawada Y, Honda T, Hanakawa S, Nakamizo S, Murata T, Ueharaguchi-Tanada Y, Ono S, Amano W, Nakajima S, Egawa G, Tanizaki H, Otsuka A, Kitoh A, Dainichi T, Ogawa N, Kobayashi Y, Yokomizo T, Arita M, Nakamura M, Miyachi Y, Kabashima K.
  • Journal Title: J Exp Med Volume: 212 Issue: 11 Pages: 1921-1930
  • DOI: 10.1084/jem.20150381
  • NAID: 120005733188
  • Peer Reviewed / Open Access
• [Journal Article] The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. (2015)
  • Author(s): Noda S, Suárez-Fariñas M, Ungar B, Kim SJ, de Guzman Strong C, Xu H, Peng X, Estrada YD, Nakajima S, Honda T, Shin JU, Lee H, Krueger JG, Lee KH, Kabashima K, Guttman-Yassky E.
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 5 Issue: 5 Pages: 1254-1264
  • DOI: 10.1016/j.jaci.2015.08.015
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling. (2015)
  • Author(s): Amano W, Nakajima S, Kunugi H, Numata Y, Kitoh A, Egawa G, Dainichi T, Honda T, Otsuka A, Kimoto Y, Yamamoto Y, Tanimoto A, Matsushita M, Miyachi Y, Kabashima K.
  • Journal Title: 10.1016/j.jaci.2015.03.051. Volume: 3 Issue: 3 Pages: 667-677
  • DOI: 10.1016/j.jaci.2015.03.051
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant