A new barrier-related gene encoding epithelial stress-induced peptide

• Project/Area Number: 18K08295
• 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: Kagawa University (2020); Kyoto University (2018-2019)
• Principal Investigator: Dainichi Teruki 香川大学, 医学部, 教授 (20423543)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 表皮 / 炎症 / バリア / アトピー性皮膚炎 / 乾癬

Outline of Final Research Achievements

The epidermis is involved in barrier, innate and adaptive immunity of the skin. We found that up-regulation of an orphan gene was shared in the skin with different, many types of inflammation. We named this molecule epithelial stress-induced peptide (ESIP). The human orthologue gene product was highly expressed in the epidermis of atopic dermatitis or psoriasis. ESIP gene transfection into normal human epidermal keratinocytes induced expression of inflammatory mediators, and gene ontology analyses showed its association to barrier formation.

Academic Significance and Societal Importance of the Research Achievements

ESIPが上皮ストレス応答のマスターレギュレーターであり、多様な臨床像を示すアトピー性皮膚炎の慢性炎症を決定づける表皮由来因子である可能性を考えた。これまでアトピー性皮膚炎などの慢性の炎症性皮膚疾患の治療標的は免疫細胞が主体であった。本研究成果により、全身の皮膚を覆う組織である表皮が、これらの皮膚疾患の新しい治療標的となる可能性を提案できる。

Research Products

• [Journal Article] Net Effects of NETs: New Concepts. (2020)
  • Author(s): Dainichi T, Nakajima S, Iwata M, Kabashima K
  • Journal Title: Journal of Investigative Dermatology Volume: 140 Issue: 5 Pages: 939-941
  • DOI: 10.1016/j.jid.2019.12.016
  • Peer Reviewed
• [Journal Article] Venous leg ulcers associated with abdominal aortic aneurysm (2020)
  • Author(s): Katsuo Kosuke、Kaku Yo、Tahara Jumpei、Yamashita Chisato、Endo Yuichiro、Egawa Gyohei、Dainichi Teruki、Kabashima Kenji
  • Journal Title: International Journal of Dermatology Volume: Epub ahead of print Issue: 7
  • DOI: 10.1111/ijd.14836
  • Peer Reviewed
• [Journal Article] Pemphigus vulgaris in a recipient and pemphigus foliaceus in a donor after allogeneic peripheral blood stem cell transplantation between two siblings (2020)
  • Author(s): Ogawa M.、Goto K.、Kanameishi S.、Dainichi T.、Kabashima K.、Tanabe H.
  • Journal Title: Journal of the European Academy of Dermatology and Venereology Volume: Epub ahead of print Issue: 8
  • DOI: 10.1111/jdv.16289
  • Peer Reviewed
• [Journal Article] Anti‐laminin γ1 pemphigoid with IgE autoantibodies (2020)
  • Author(s): Komatsu‐Fujii T.、Dainichi T.、Kaku Y.、Murata T.、Nomura T.、Kabashima K.
  • Journal Title: Journal of the European Academy of Dermatology and Venereology Volume: Epub ahead of print Issue: 6
  • DOI: 10.1111/jdv.16259
  • Peer Reviewed
• [Journal Article] Efficacy of intravenous immunoglobulins for laryngopharyngeal lesions and upper airway obstruction in epidermolysis bullosa acquisita (2019)
  • Author(s): Komatsu‐Fujii T.、Honda T.、Tahara J.、Yamashita C.、Oguma T.、Dainichi T.、Kabashima K.
  • Journal Title: Journal of the European Academy of Dermatology and Venereology Volume: 34 Issue: 3
  • DOI: 10.1111/jdv.16080
  • Peer Reviewed
• [Journal Article] Amelanotic melanoma of the nail apparatus with regression previously diagnosed as melanoma of unknown primary site with a lymph node metastasis: A case report (2019)
  • Author(s): Tahara Jumpei、Kaku Yo、Takimoto Ito Riko、Irie Hiroyuki、Endo Yuichiro、Egawa Gyohei、Dainichi Teruki、Kabashima Kenji
  • Journal Title: The Journal of Dermatology Volume: 47 Issue: 2
  • DOI: 10.1111/1346-8138.15158
  • Peer Reviewed
• [Journal Article] APOBEC3 regulates keratinocyte differentiation and expression of Notch3 (2019)
  • Author(s): Dainichi Teruki、Nakano Yuri、Wakae Kousho、Otsuka Masayuki、Muramatsu Masamichi、Kabashima Kenji
  • Journal Title: Experimental Dermatology Volume: 28 Issue: 11 Pages: 1341-1347
  • DOI: 10.1111/exd.14019
  • Peer Reviewed
• [Journal Article] Percutaneous sensitization is limited by in situ inhibition of cutaneous dendritic cell migration through skin-resident regulatory T cells. (2019)
  • Author(s): Hanakawa S, Kitoh A, Shibuya R, Dainichi T, Nomura T, Honda T, Egawa G, Otsuka A, Nakajima S, Fujita M, Kabashima K.
  • Journal Title: J Allergy Clin Immunol. 2019 Volume: 144(5) Issue: 5 Pages: 1343-1353
  • DOI: 10.1016/j.jaci.2019.05.033
  • Peer Reviewed
• [Journal Article] Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis. (2019)
  • Author(s): Sakurai K, Dainichi T, Garcet S, Tsuchiya S, Yamamoto Y, Kitoh A, Honda T, Nomura T, Egawa G, Otsuka A, Nakajima S, Matsumoto R, Nakano Y, Otsuka M, Iwakura Y, Grinberg-Bleyer Y, Ghosh S, Sugimoto Y, Guttman-Yassky E, Krueger JG, Kabashima K.
  • Journal Title: J Allergy Clin Immunol Volume: 144(4) Issue: 4 Pages: 1036-1049
  • DOI: 10.1016/j.jaci.2019.06.019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model (2019)
  • Author(s): Ono S, Egawa G, Nomura T, Kitoh A, Dainichi T, Otsuka A, Nakajima S, Amagai M, Matsumoto F, Yamamoto M, Kubota Y, Takai T, Honda T, Kabashima K.
  • Journal Title: Nat Commun Volume: 10(1) Issue: 1 Pages: 4432-4432
  • DOI: 10.1038/s41467-019-12232-3
  • NAID: 120006731596
  • Peer Reviewed / Open Access
• [Journal Article] Murine neonatal skin mast cells are phenotypically immature and minimally sensitized with transplacentally transferred IgE. (2019)
  • Author(s): Honda Y, Ono S, Honda T, Kataoka TR, Egawa G, Kitoh A, Otsuka A, Nakajima S, Nomura T, Dainichi T, Kabashima K.
  • Journal Title: J Allergy Clin Immunol. 2019 Volume: 144(2) Issue: 2 Pages: 617-620
  • DOI: 10.1016/j.jaci.2019.05.011
  • Peer Reviewed
• [Journal Article] Progressive Erythroderma without Malignancy in the Skin: A Quiz (2019)
  • Author(s): Irie H、Dainichi T、Kaku Y、Kabashima K
  • Journal Title: Acta Dermato Venereologica Volume: 99 Issue: 9 Pages: 841-843
  • DOI: 10.2340/00015555-3206
  • Peer Reviewed
• [Journal Article] Predictive factors of response to pulse methylprednisolone therapy in patients with alopecia areata: A follow‐up study of 105 Japanese patients (2019)
  • Author(s): Fujii Hiroko、Endo Yuichiro、Dainichi Teruki、Otsuka Atsushi、Fujisawa Akihiro、Tanioka Miki、Miyachi Yoshiki、Kabashima Kenji
  • Journal Title: The Journal of Dermatology Volume: 46 Issue: 6 Pages: 522-525
  • DOI: 10.1111/1346-8138.14871
  • Peer Reviewed
• [Journal Article] Immune Control by TRAF6-Mediated Pathways of Epithelial Cells in the EIME (Epithelial Immune Microenvironment) (2019)
  • Author(s): Dainichi Teruki、Matsumoto Reiko、Mostafa Alshimaa、Kabashima Kenji
  • Journal Title: Frontiers in Immunology Volume: 10 Pages: 1107-1107
  • DOI: 10.3389/fimmu.2019.01107
  • NAID: 120006644062
  • Peer Reviewed / Open Access
• [Journal Article] The epithelial immune microenvironment (EIME) in atopic dermatitis and psoriasis (2018)
  • Author(s): Dainichi Teruki、Kitoh Akihiko、Otsuka Atsushi、Nakajima Saeko、Nomura Takashi、Kaplan Daniel H.、Kabashima Kenji
  • Journal Title: Nature Immunology Volume: 19 Issue: 12 Pages: 1286-1298
  • DOI: 10.1038/s41590-018-0256-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Interaction of Psoriasis and Bullous Diseases (2018)
  • Author(s): Dainichi Teruki、Kabashima Kenji
  • Journal Title: Frontiers in Medicine Volume: 5 Pages: 1-9
  • DOI: 10.3389/fmed.2018.00222
  • NAID: 120006591378
  • Peer Reviewed
• [Journal Article] Epithelial TRAF6 drives IL-17?mediated psoriatic inflammation (2018)
  • Author(s): Matsumoto Reiko、Dainichi Teruki、Tsuchiya Soken、Nomura Takashi、Kitoh Akihiko、Hayden Matthew S.、Ishii Ken J.、Tanaka Mayuri、Honda Tetsuya、Egawa Gyohei、Otsuka Atsushi、Nakajima Saeko、Sakurai Kenji、Nakano Yuri、Kobayashi Takashi、Sugimoto Yukihiko、Kabashima Kenji
  • Journal Title: JCI Insight Volume: 3 Issue: 15 Pages: 1-14
  • DOI: 10.1172/jci.insight.121175
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transient elevation of cytoplasmic calcium ion concentration at a single cell level precedes morphological changes of epidermal keratinocytes during cornification (2018)
  • Author(s): Murata Teruasa、Honda Tetsuya、Egawa Gyohei、Yamamoto Yasuo、Ichijo Ryo、Toyoshima Fumiko、Dainichi Teruki、Kabashima Kenji
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 1-10
  • DOI: 10.1038/s41598-018-24899-7
  • NAID: 120006522872
  • Peer Reviewed / Open Access
• [Journal Article] Mild dystrophic epidermolysis bullosa associated with homozygous gene mutation c.6216+5G>T in type VII collagen ultrastructurally suggestive of the decreased number of anchoring fibrils (2018)
  • Author(s): Komori Takaya、Dainichi Teruki、Otsuka Atsushi、Nakano Hajime、Sawamura Daisuke、Ishida-Yamamoto Akemi、Kabashima Kenji
  • Journal Title: The Journal of Dermatology Volume: 印刷中 Issue: 11
  • DOI: 10.1111/1346-8138.14337
  • Peer Reviewed
• [Journal Article] p.Glu477Lys mutation in keratin 5 is not necessarily mortal in generalized severe epidermolysis bullosa simplex (2018)
  • Author(s): Komori Takaya、Dainichi Teruki、Masuno Yuka、Otsuka Atsushi、Nakano Hajime、Sawamura Daisuke、Ishida-Yamamoto Akemi、Kabashima Kenji
  • Journal Title: The Journal of Dermatology Volume: 印刷中 Issue: 8
  • DOI: 10.1111/1346-8138.14258
  • Peer Reviewed
• [Presentation] アトピー性皮膚疾患と epithelial-immune microenvironment (EIME) (2019)
  • Author(s): 大日 輝記
  • Organizer: 第68回日本アレルギー学会学術大会シンポジウム
  • Invited
• [Presentation] Topical p38 MAPK Activation Induces Psoriatic Dermatitis (2019)
  • Author(s): Kenji Sakurai, Teruki Dainichi, Sandra Garcet, Soken Tsuchiya, Yoichiro Iwakura, Sankar Ghosh, Yukihiko Sugimoto, Emma Guttman-Yassky, James G. Krueger, Kenji Kabashima
  • Organizer: Keystone Simposia, Skin Health and Disease: Immune, Epithelial and Microbiome Crosstalk (D4), Hannover, Germany
  • Int'l Joint Research
• [Presentation] APOBEC3 regulates NOTCH3 expression and keratinocyte differentiation (2018)
  • Author(s): Teruki Dainichi, Yuri Nakano, Kousho Wakae, Masayuki Otsuka, Masamichi Muramatsu, Kenji Kabashima
  • Organizer: International Investigative Dermatology Meeting 2018, Orlando, Florida
  • Int'l Joint Research