Establishment of skin microbe-host immunity analysis method based on understanding the concept of "superorganism"

• Project/Area Number: 16H06252
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Chiba University
• Principal Investigator: Matsuoka Yuumi 千葉大学, 大学院医学研究院, 講師 (10402067)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000); Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2016: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
• Keywords: 皮膚細菌叢 / 免疫応答 / 超個体 / 黄色ブドウ球菌 / カンジタ / 皮膚常在菌叢 / 黄色ブトウ球菌 / 皮膚常在細菌叢 / カンジダ / 皮膚 / 感染症 / 免疫 / 微生物

Outline of Final Research Achievements

Microbiome analysis is widely performed in recent years in the intestinal tract, skin, etc., and the contribution of microbiome to the diseases is becoming clearer. When we analysis the microbe-immune response in the skin, we have to analyze not only the host immune responses and bacterial community, but also fungal and viral community. However, there was no good model for microbial immune response analysis targeting whole symbiotic microorganisms. Therefore, we aim to establish a new model for analyzing the microbe-immune response in the skin. In this study, we found that IL-17-producing cells in our S. aureus infection model were ILC3 and gdT cells. In addition, a phenotypic differences were obvious in keratinocyte-specific MyD88knockout and IL-1/36 deficient mice.We also established a new inflammatory skin model with pathogenic fungi such as C. albicans and M. furfur.

Academic Significance and Societal Importance of the Research Achievements

病原微生物による皮膚炎発症のメカニズムについてはこれまで良い動物モデルがなく、詳細は明らかではなかった。我々が先行研究で確立した経表皮的黄色ブドウ球菌感染マウスモデルを用いて皮膚の最外層における病原微生物に対する宿主応答を検討することで、新たな病原微生物による皮膚炎発症のメカニズムを明らかにできたと考えている。

Research Products

• [Int'l Joint Research] University of Michigan/NIH(米国)
• [Journal Article] Application of an agr-Specific Antivirulence Compound as Therapy for Staphylococcus aureus-Induced Inflammatory Skin Disease. (2018)
  • Author(s): Baldry M, Nakamura Y, Nakagawa S, Frees D, Matsue H, Nunez G, Ingmer H.
  • Journal Title: J Infect Dis Volume: 218(6) Issue: 6 Pages: 1009-1013
  • DOI: 10.1093/infdis/jiy259
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Streptococcal Cysteine Protease-Mediated Cleavage of Desmogleins Is Involved in the Pathogenesis of Cutaneous Infection (2018)
  • Author(s): Sumitomo Tomoko、Mori Yasushi、Nakamura Yuumi、Honda-Ogawa Mariko、Nakagawa Seitaro、Yamaguchi Masaya、Matsue Hiroyuki、Terao Yutaka、Nakata Masanobu、Kawabata Shigetada
  • Journal Title: Front Cell Infect Microbiol Volume: 8 Pages: 10-10
  • DOI: 10.3389/fcimb.2018.00010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Staphylococcus aureus Virulent PSMα Peptides Induce Keratinocyte Alarmin Release to Orchestrate IL-17-Dependent Skin Inflammation (2017)
  • Author(s): Nakagawa S, Matsumoto M, Katayama Y, Oguma R, Wakabayashi S, Nygaard T, Saijo S, Inohara N, Otto M, Matsue H, Nunez G, Nakamura Y
  • Journal Title: Cell Host Microbe Volume: 22(5) Issue: 5 Pages: 667-677
  • DOI: 10.1016/j.chom.2017.10.008
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Cutaneous retention of Staphylococcus agr virulence promotes atopic dermatitis development (2018)
  • Author(s): Yuumi Matsuoka-Nakamura
  • Organizer: The 2nd Chiba University-UC San Diego Symposium “Mucosal Immunology, Allergy and Vaccine”
  • Invited
• [Presentation] PSMs as a key virulence in Staphylococcus aureus-induced skin inflammation though IL-36 and IL-1 release from keratinocyte (2017)
  • Author(s): Nakagawa S, Nakamura Y, Nunez G, Matsue H
  • Organizer: 76th SID Annual Meeting
  • Int'l Joint Research
• [Presentation] Understanding the link between Staphylococcus aureus colonization and skin disease (2017)
  • Author(s): Nakamura Y
  • Organizer: 第46回日本免疫学会学術集会
  • Invited
• [Presentation] Staphylococcus aureus PSMa peptides induce keratinocyte alarmin release to orchestrate IL-17 dependent skin inflammation (2017)
  • Author(s): Nakagawa S, Nakamura Y, Matsumoto M, Katayama Y, Oguma R, Nunez G, Matsue H
  • Organizer: 第42回日本研究皮膚科学会
• [Presentation] Staphylococcus PSMα induces IL-17-dependent skin inflammation through IL-36 and IL-1 secretion from keratinocyte (2016)
  • Author(s): Nakagawa S, Nakamura Y, Oguma R, Katayama Y, Matsumoto M, Nunez G, Matsue H
  • Organizer: The 41st Annual Meeting of Japanese Society for Investigative Dermatology