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Elucidation of regulation mechanism of ocular surface inflammation by IKZF1

Research Project

Project/Area Number 16K11327
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

UETA MAYUMI  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (60398386)

Research Collaborator Nishigaki Hiromi  
Ohsako Seiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsIKZF1 / 皮膚粘膜炎症 / 眼表面炎症 / 上皮細胞 / 炎症制御 / 眼表面上皮 / 眼免疫学
Outline of Final Research Achievements

We found that human epidermis and conjunctival epithelium expressed IKZF1, and in PHCjECs and HEKa, the expression of IKZF1 mRNA was upregulated by stimulation with polyI:C, a TLR3 ligand. In Ikzf1 Tg, we observed dermatitis and mucosal inflammation including the ocular surface. In contact dermatitis model, inflammatory infiltrates in the skin of Ikzf1 Tg were significantly increased compared with wild type. Microarray analysis showed that Lcn2, Adh7, Epgn, Ifi202b, Cdo1, Gpr37, Duoxa1, Tnfrsf4, and Enpp5 genes were significantly upregulated in the epidermis of Ikzf1 Tg compared with wild type.

Academic Significance and Societal Importance of the Research Achievements

全ゲノム関連解析によりIKZF1遺伝子が皮膚粘膜炎症性疾患の発症に大きく関与していることが研究代表者の以前の研究で明らかとなっている。本研究は、生体において、IKZF1遺伝子が皮膚粘膜炎症を制御していることを世界で初めて発見した重要な研究である。本研究により、IKZF1は皮膚粘膜炎症疾患に対する新規治療薬の標的となると考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results)

  • [Journal Article] Distinctly regulated functions and mobilization of CD11c-positive cells elicited by TLR3- and IPS-1 signaling in the cornea2019

    • Author(s)
      Ueta Mayumi、Hamuro Junji、Ohsako Suzuko、Kinoshita Shigeru
    • Journal Title

      Immunology Letters

      Volume: 206 Pages: 49-53

    • DOI

      10.1016/j.imlet.2018.12.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Results of Detailed Investigations Into Stevens-Johnson Syndrome With Severe Ocular Complications2018

    • Author(s)
      Ueta Mayumi
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 59 Issue: 14 Pages: DES183-DES183

    • DOI

      10.1167/iovs.17-23537

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mucocutaneous inflammation in the Ikaros Family Zinc Finger 1-keratin 5-specific transgenic mice2018

    • Author(s)
      Ueta M, Hamuro J, Nishigaki H, Nakamura N, Shinomiya K, Mizushima K, Hitomi Y, Tamagawa-Mineoka R, Yokoi N, Naito Y, Tokunaga K, Katoh N, Sotozono C, Kinoshita S.
    • Journal Title

      Allergy

      Volume: 73 Issue: 2 Pages: 395-404

    • DOI

      10.1111/all.13308

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide association study using the ethnicity-specific Japonica array: identification of new susceptibility loci for cold medicine-related Stevens-Johnson syndrome with severe ocular complications2017

    • Author(s)
      Mayumi Ueta , Hiromi Sawai*, Ryosei Shingaki, Yusuke Kawai, Chie Sotozono, Kaname Kojima, Kyung-Chul Yoon, Mee Kum Kim, Kyoung Yul Seo, Choun-Ki Joo, et al. *Contributed equally with the first author
    • Journal Title

      Journal of Human Genetics

      Volume: 62 Issue: 4 Pages: 485-489

    • DOI

      10.1038/jhg.2016.160

    • NAID

      40021158280

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human Leukocyte Antigen Class I Genes Associated With Stevens-Johnson Syndrome and Severe Ocular Complications Following Use of Cold Medicine in a Brazilian Population.2017

    • Author(s)
      1.Wakamatsu TH, Ueta M, Tokunaga K, Okada Y, Loureiro RR, Costa KA, Sallum JM, Milhomens JA, Inoue C, Sotozono C, Gomes JÁ, Kinoshita S
    • Journal Title

      JAMA Ophthalmol.

      Volume: in press Issue: 4 Pages: 355-355

    • DOI

      10.1001/jamaophthalmol.2017.0074

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Plasma Lipid Profiling of Patients with Chronic Ocular Complications Caused by Stevens Johnson Syndrome/Toxic Epidermal Necrolysis2016

    • Author(s)
      Saito K, Ueta M, Maekawa K, Sotozono C, Kinoshita S, Saito Y
    • Journal Title

      PLoS One

      Volume: 11 Issue: 11 Pages: e0167402-e0167402

    • DOI

      10.1371/journal.pone.0167402

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Regulation of Ikzf1 inducible genes in epidermis2018

    • Author(s)
      Mayumi Ueta, Hiromi Nishigaki, Suzuko Ohsako, Shigeru Kinoshita.
    • Organizer
      The European Academy of Allergy and Clinical Immunology (EAACI) Congress 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of Ikzf1 inducible genes by TLR3 and IPS-12018

    • Author(s)
      Mayumi Ueta, Hiromi Nishigaki, Kiyoko Oosako, Shigeru Kinoshita
    • Organizer
      2018 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinctly regulated functions and mobilization of CD11c-positive cells by TLR3- and IPS-1 signaling in the cornea2018

    • Author(s)
      Mayumi Ueta, Junji Hamuro, Shigeru Kinoshita
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Ocular Surface inflammation is regulated by innate immunity ----- focusing on Stevens-Johnson syndrome -----2017

    • Author(s)
      MAYUMI UETA
    • Organizer
      2017 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Elevated Expression of Ikaros Family Zinc Finger 1 (IKZF1) Exacerbates Mucocutaneous Inflammation2017

    • Author(s)
      Mayumi Ueta, Junji Hamuro, Naomi Nakamura,Risa Tamagawa-Mineoka, Norito Katoh, Shigeru Kinoshita.
    • Organizer
      The European Academy of Allergy and Clinical Immunology (EAACI) Congress 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Skin Inflammation of Ikzf1-EGFP Transgenic Mice2017

    • Author(s)
      MAYUMI Ueta, Junji Hamuro, Shigeru Kinoshita,
    • Organizer
      The EAACI/ESCD Skin Allergy Meeting, SAM
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 感冒薬関連SJS疾患関連遺伝子IKZF1による皮膚粘膜炎症制御2017

    • Author(s)
      上田真由美、羽室淳爾、中村直美、峠岡理沙、加藤則人、人見祐基、徳永勝士、木下茂.
    • Organizer
      日本人類遺伝学会 第61回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] HLA and Stevens Johnson Syndrome2017

    • Author(s)
      MAYUMI UETA
    • Organizer
      I PANCORNEA CONGRESS
    • Place of Presentation
      米国、マイアミ
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Pathology of Stevens-Johnson Syndrome2016

    • Author(s)
      Mayumi Ueta
    • Organizer
      2nd Chulalongkorn Eye Center-Kyoto Prefectural University of Medicine Joint meeting
    • Place of Presentation
      タイ、バンコク
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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