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

• Project/Area Number: 18K08310
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Tokyo Women's Medical University (2019-2023); Keio University (2018)
• Principal Investigator: 荒尾 知子 (梅垣 知子 / 梅垣知子) 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: ¥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)
• Keywords: CHILD症候群 / 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 Annual Research Achievements

CHILD症候群モデルマウス(K5-Cre-NSDHL+/--CD1a-tg)の作成
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
マウスES細胞にNSDHLターゲッティングベクターをエレクトロポレーションにて導入し、コロニーのピックアップを行った。ES細胞のスクリーニング後、胚盤胞(BALB/c)への注入を行い、NSDHLキメラマウスを作成した。ES細胞(毛が黒色)とホスト胚（BALB/c）（アルピノ）とのキメラF1マウス（♂）と、B6（黒色）マウスと交配し、黒色のF２マウス♀5匹について、ジェノタイピングを行った。キメラマウスの尾からCica GeneusトータルDNAプレップキットを用いてDNAを抽出した。ターゲットベクターを挟むように数カ所primerを設定してPCRを行い、ジェノタイプを確認した。さらにNSDHLキメラマウスとK5-Creを掛け合わせてNSDHL変異を持つK5-Cre-NSDHLfloxを作成し、表皮特異的にNSDHLをノックアウトした。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。さらに、ヒトCD1aトランスジェニックマウス(CD1a-tg)(Kim JH, et al. Nat Immunol, 2016)について、耳介に2％ウルシオールを塗布し、皮膚炎誘発が再現できるか確認を行ったが、野生型のマウスと比較して耳介の厚さ（腫脹）については有意差を認めなかった。

Research Products

• [Journal Article] Histological analysis of psoriasiform eruption associated with myelin oligodendrocyte glycoprotein antibody-associated disease (2024)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Superimposition of checkerboard distribution of ephelides and neurofibromas in a patient with segmental neurofibromatosis (2022)
  • 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
  • Peer Reviewed
• [Journal Article] Two cases of acquired lymphangioma: Dermoscopic-histopathologic correlation between irregular vessels on lacunae (2021)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Two case reports of Mycobacterium marinum infection with psoriatic arthritis treated by tumor necrosis factor‐α inhibitors (2020)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Eosinophilic pustular folliculitis with palmoplantar lesions and nail deformity (2020)
  • 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
  • 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 receptor (2019)
  • 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
  • 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 Heterozygotes (2019)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alopecia areata multiplex following autologous dermal micrograft injection for treatment of androgenetic alopecia (2019)
  • 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
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Successful treatment with secukinumab of three psoriatic patients undergoing dialysis (2019)
  • 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
  • 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.
  • Int'l Joint Research