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Mechanism of lipid antigen presentation via CD1a and induction of skin inflammation

Research Project

Project/Area Number 18K08310
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionTokyo Women's Medical University (2019-2023)
Keio University (2018)

Principal Investigator

Arao Noriko  東京女子医科大学, 医学部, 准教授 (80397629)

Co-Investigator(Kenkyū-buntansha) 久保 亜紀子  神戸大学, 医学研究科, 特命講師 (50455573)
久保 亮治  慶應義塾大学, 医学部(信濃町), 准教授 (70335256)
Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordsCHILD症候群 / 皮膚炎 / ケブネル現象 / 乾癬様皮疹 / CHILD症候群モデルマウス / NSDHL / コレステロール代謝物 / モデルマウス / 乾癬様皮膚炎 / コレステロール合成 / CD1a
Outline of Final Research Achievements

We successfully created skin epidermis-specific NSDHL conditional knockout mice (K5-Cre-NSDHLflox). NSDHL targeting vector was introduced into mouse ES cells via electroporation, followed by colony picking. After screening of ES cells, injection into blastocysts (BALB/c) was performed to generate NSDHL chimeric mice. Chimeric F1 mice (♂) with ES cells (black hair) and host embryos (BALB/c, albino) were crossed with B6 mice (black) and genotyped for 5 female F2 mice with black coat color. DNA was extracted from the tails of chimeric mice and genotyping was confirmed. Furthermore, NSDHL mutant mice carrying K5-Cre were generated by crossing NSDHL chimeric mice with K5-Cre, resulting in skin epidermis-specific NSDHL knockout.

Academic Significance and Societal Importance of the Research Achievements

表皮特異的NSDHLコンディショナルノックアウトマウス(K5-Cre-NSDHLflox)の作成することに成功した。表皮特異的NSDHLコンディショナルノックアウトマウスの皮膚にモザイク状に脱毛を伴うphenotypeが見られ、3匹のマウスについてその部位の皮膚を生検して、皮膚のHE染色を行った。脱毛部では表皮の菲薄化と毛包構造の消失があり、一方で有毛部では、皮膚炎を想起させる角質層の錯角化を認めた。今後、CHILD症候群における皮膚炎発症のメカニズム解明に有益な成果と考えられる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (12 results)

All 2024 2023 2022 2021 2020 2019

All Journal Article (11 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 11 results,  Open Access: 6 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Histological analysis of psoriasiform eruption associated with myelin oligodendrocyte glycoprotein antibody-associated disease2024

    • Author(s)
      Itoi-Ochi Saori、Kurosaki Yukiho、Ota Asako、Miyazaki Akiko、Hosokawa Akiko、Nakano Misa、Takahashi Toshiyuki、Umegaki-Arao Noriko、Fujimoto Manabu
    • Journal Title

      JAAD Case Reports

      Volume: 46 Pages: 1-4

    • DOI

      10.1016/j.jdcr.2023.12.026

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Palmar whitish change after water exposure in a familial mild case of loricrin keratoderma (loricrin ichthyosis)2022

    • Author(s)
      Saito Sonoko、Tanaka Ryo、Ono Noriko、Umegaki‐Arao Noriko、Sasaki Takashi、Aoki Satomi、Amagai Masayuki、Kubo Akiharu
    • Journal Title

      The Journal of Dermatology

      Volume: 49 Issue: 11

    • DOI

      10.1111/1346-8138.16481

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Superimposition of checkerboard distribution of ephelides and neurofibromas in a patient with segmental neurofibromatosis2022

    • Author(s)
      Iriki Hisato、Umegaki-Arao Noriko、Kakuta Risa、Fujita Harumi、Aoki Satomi、Amagai Masayuki、Sasaki Takashi、Hamamoto Yasuo、Nakayama Robert、Kubo Akiharu
    • Journal Title

      JAAD Case Reports

      Volume: 25 Pages: 89-92

    • DOI

      10.1016/j.jdcr.2022.05.025

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Two cases of acquired lymphangioma: Dermoscopic-histopathologic correlation between irregular vessels on lacunae2021

    • Author(s)
      Komatsu H, Umegaki-Arao N, Futei Y, Iwabuchi E, Ishizaki S, Tanaka M.
    • Journal Title

      J Dermatol.

      Volume: 48(10) Issue: 10

    • DOI

      10.1111/1346-8138.16056

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Two case reports of Mycobacterium marinum infection with psoriatic arthritis treated by tumor necrosis factor‐α inhibitors2020

    • Author(s)
      Furuichi Yuki、Ito Yoshihiro、Tanese Keiji、Mukai Miho、Uwamino Yoshifumi、Hasegawa Naoki、Amagai Masayuki、Umegaki‐Arao Noriko
    • Journal Title

      The Journal of Dermatology

      Volume: 48 Issue: 2

    • DOI

      10.1111/1346-8138.15674

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Eosinophilic pustular folliculitis with palmoplantar lesions and nail deformity2020

    • Author(s)
      Umegaki‐Arao Noriko、Tanemoto Sae、Tanese Keiji、Kubo Akiharu、Takahashi Hayato、Kurihara Yuichi、Yanagisawa Erika、Kameyama Kaori、Amagai Masayuki、Saito Masataka
    • Journal Title

      The Journal of Dermatology

      Volume: 47 Issue: 10

    • DOI

      10.1111/1346-8138.15503

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A nonepidermolytic keratinocytic epidermal naevus associated with a postzygotic mutation in the gene encoding epidermal growth factor receptor2019

    • Author(s)
      Umegaki‐Arao N.、Ono N.、Tanaka R.、Sasaki T.、Fujita H.、Shiohama A.、Aoki S.、Amagai M.、Kubo A.
    • Journal Title

      British Journal of Dermatology

      Volume: - Issue: 5 Pages: 1303-1305

    • DOI

      10.1111/bjd.18729

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clonal Expansion of Second-Hit Cells with Somatic Recombinations or C>T Transitions Form Porokeratosis in MVD or MVK Mutant Heterozygotes2019

    • Author(s)
      Kubo Akiharu、Sasaki Takashi、Suzuki Hisato、Shiohama Aiko、Aoki Satomi、Sato Showbu、Fujita Harumi、Ono Noriko、Umegaki-Arao Noriko、Kawai Tomoko、Nakabayashi Kazuhiko、Hata Kenichiro、Yamada Daisuke、Matsubara Yoichi、Kosaki Kenjiro、Amagai Masayuki
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 139 Issue: 12 Pages: 2458-2466.e9

    • DOI

      10.1016/j.jid.2019.05.020

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alopecia areata multiplex following autologous dermal micrograft injection for treatment of androgenetic alopecia2019

    • Author(s)
      Toshima S.、Kurihara Y.、Wang E.H.C.、Nomura H.、Hayashi Y.、Christiano A.M.、Amagai M.、Umegaki‐Arao N.
    • Journal Title

      Journal of the European Academy of Dermatology and Venereology

      Volume: 33 Issue: 11

    • DOI

      10.1111/jdv.15701

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alopecia in Cronkhite?Canada syndrome: Is it truly telogen effluvium?2019

    • Author(s)
      Horikawa Hiroto、Hirai Ikuko、Umegaki‐Arao Noriko、Amagai Masayuki、Saito Masataka
    • Journal Title

      Australasian Journal of Dermatology

      Volume: 60 Issue: 4

    • DOI

      10.1111/ajd.13073

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Successful treatment with secukinumab of three psoriatic patients undergoing dialysis2019

    • Author(s)
      Mukai Miho、Kurihara Yuichi、Ito Yoshihiro、Shintani Yuka、Takahashi Hayato、Kubo Akiharu、Amagai Masayuki、Umegaki‐Arao Noriko
    • Journal Title

      The Journal of Dermatology

      Volume: 47 Issue: 1

    • DOI

      10.1111/1346-8138.15132

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] A non-epidermolytic epidermal nevus associated with a postzygotic EGFR mutation.2023

    • Author(s)
      Umegaki-Arao N, Ono N, Tanaka R, Sasaki T, Fujita H, Shiohama A, Amagai M, Kubo A.
    • Organizer
      1st. International Societies for Investigative Dermatology Meeting, Tokyo, Japan, 2023.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2025-01-30  

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