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Elucidation of mechanism underlying intrinsic atopic dermatitis induced by deficiency of sprabasin co-expressed in skin and intestine

Research Project

Project/Area Number 17H04241
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Tokura Yoshiki  浜松医科大学, 医学部, 特任教授 (00172156)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords皮膚科学 / 炎症学 / アレルギー / 免疫学 / 皮膚免疫
Outline of Final Research Achievements

Suprabasin (SBSN) is expressed in epidermis and epithelial cells of the upper digestive tract where metals such as nickel are absorbed. SBSN level was decreased in the stratum corneum and serum of atopic dermatitis (AD) patients, especially in intrinsic AD, which is characterized by metal allergy. By using SBSN-null (Sbsn-/-) mice, we investigated the outcome of SBSN deficiency. Sbsn-/- mice exhibited skin barrier dysfunction on embryo, but after birth, their barrier function was not perturbed. Sbsn-/- mice showed rather lower contact hypersensitivity (CHS) responses to haptens than did wild-type mice. The blood nickel (Ni) level after oral feeding of nickel was significantly higher in Sbsn-/- mice, and CHS to Ni was elevated in Sbsn-/- mice under Ni-loading condition. The completely SBSN deficient mice retain normal barrier function, but harbor abnormal upper digestive tract epithelium that promotes Ni absorption and high CHS to nickel, sharing the features of intrinsic AD.

Academic Significance and Societal Importance of the Research Achievements

学術的意義として、病態が不明の内因性ADの原因の一つに、SBSN欠乏がある可能性を提起した。従来、内因性ADは血清IgE値が高くないサブタイプとして不思議な存在であった。若い女性に多く、どういう訳か金属アレルギーの頻度が高い。バリア機能も損なわれていない。これがSBSN欠乏によってもたらされる場合があることを示唆した。これは社会的意義として、若い女性に多い内因性ADの解明に繋がることにより、患者の不安感を払拭し、将来的な治療の開発に道を開いた。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (42 results)

All 2021 2020 2019 2018 2017 2015 Other

All Journal Article (23 results) (of which Peer Reviewed: 20 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 12 results,  Invited: 2 results) Book (4 results) Remarks (1 results)

  • [Journal Article] Direct and indirect action modes of acetylcholine in cholinergic urticaria2021

    • Author(s)
      Tokura Y
    • Journal Title

      Allergology International

      Volume: 70 Issue: 1 Pages: 39-44

    • DOI

      10.1016/j.alit.2020.05.006

    • NAID

      130007966773

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathophysiology of Skin Resident Memory T Cells2021

    • Author(s)
      Tokura Y、Phadungsaksawasdi P、Kurihara K、Fujiyama T、Honda T
    • Journal Title

      Front Immunol

      Volume: 11

    • DOI

      10.3389/fimmu.2020.618897

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunological Properties of Atopic Dermatitis-Associated Alopecia Areata2021

    • Author(s)
      1.Kageyama R, Ito T, Hanai S, Morishita N, Nakazawa S, Fujiyama T, Honda T, Tokura Y
    • Journal Title

      Int J Mol Sci

      Volume: 22 Issue: 5 Pages: 2618-2629

    • DOI

      10.3390/ijms22052618

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PD-1 expression defines epidermal CD8+CD103+ T cells preferentially producing IL-17A and using skewed TCR repertoire in psoriasis2021

    • Author(s)
      Phadungsaksawasdi Pawit、Fujiyama Toshiharu、Kurihara Kazuo、Ito Taisuke、Honda Tetsuya、Tokura Yoshiki
    • Journal Title

      J Invest Dermatol

      Volume: - Issue: 10 Pages: 2426-2435.e5

    • DOI

      10.1016/j.jid.2021.03.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集 新時代を迎えたアトピー性皮膚炎 臨床例 内因性アトピー性皮膚炎2020

    • Author(s)
      戸倉新樹
    • Journal Title

      皮膚病診療

      Volume: 42 Issue: 10 Pages: 856-860

    • DOI

      10.24733/pd.0000002154

    • ISSN
      0387-7531
    • Year and Date
      2020-10-01
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Spectrum of lgG4-related skin disease and differential diagnoses2020

    • Author(s)
      Tokura Y
    • Journal Title

      Hong Kong J. Dermatology Venereol

      Volume: 28 Pages: 100-110

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasmacytoid dendritic cells as a possible key player to initiate alopecia areata in the C3H/HeJ mouse2020

    • Author(s)
      Ito T, Suzuki T, Sakabe JI, Funakoshi A, Fujiyama T, Tokura Y
    • Journal Title

      Allergology International

      Volume: 69 Issue: 1 Pages: 121-131

    • DOI

      10.1016/j.alit.2019.07.009

    • NAID

      130007788680

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Confusion in determination of two types of cutaneous adverse reactions to drugs, maculopapular eruption and erythema multiforme, among the experts: A proposal of standardized terminology2020

    • Author(s)
      Hashizume H, Abe R, Azukizawa H, Fujiyama T, Hama N, Mizukawa Y, Morita E, Nakagawa Y, Nakajima S, Niihara H, Teraki Y, Tohyama M, Watanabe H, Tokura Y, Drug Allergy Database Committee in Japanese Cutaneous Immunology and Allergy Association
    • Journal Title

      J Dermatol

      Volume: 47 Issue: 2 Pages: 169-173

    • DOI

      10.1111/1346-8138.15164

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Skin Infiltration of Pathogenic Migratory and Resident T Cells Is Decreased by Secukinumab Treatment in Psoriasis2020

    • Author(s)
      Fujiyama T, Umayahara T, Kurihara K, Shimauchi T, Ito T, Aoshima M, Otobe M, Hashizume H, Yagi H, Tokura Y
    • Journal Title

      J Invest Dermatol

      Volume: 140 Issue: 10 Pages: 2073-2076

    • DOI

      10.1016/j.jid.2020.02.024

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protective role of Galectin‐7 for skin barrier impairment in atopic dermatitis2020

    • Author(s)
      Umayahara Takatsune、Shimauchi Takatoshi、Iwasaki Manami、Sakabe Jun‐ichi、Aoshima Masahiro、Nakazawa Shinsuke、Yatagai Tsuyoshi、Yamaguchi Hayato、Phadungsaksawasdi Pawit、Kurihara Kazuo、Tokura Yoshiki
    • Journal Title

      Clinical & Experimental Allergy

      Volume: 50 Issue: 8 Pages: 922-931

    • DOI

      10.1111/cea.13672

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCR5 is a novel target for the treatment of experimental alopecia areata.2020

    • Author(s)
      Ito T, Suzuki T, Funakoshi A, Fujiyama T, Tokura Y.
    • Journal Title

      J Cutan Immunol Allerg

      Volume: 3 Issue: 2 Pages: 24-32

    • DOI

      10.1002/cia2.12092

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suprabasin-null mice retain skin barrier function and show high contact hypersensitivity to nickel upon oral nickel loading2020

    • Author(s)
      Nakazawa S, Shimauchi T, Funakoshi A, Aoshima M, Phadungsaksawasdi P, Sakabe J, Asakawa S, Hirasawa N, Ito T, Tokura Y
    • Journal Title

      Sci Rep

      Volume: 10 Issue: 1

    • DOI

      10.1038/s41598-020-71536-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 病態の新しい考え方/内因性・外因性アトピー性皮膚炎とは2019

    • Author(s)
      戸倉新樹
    • Journal Title

      皮膚科の臨床 臨時増刊号(変わりつつあるアトピー性皮膚炎の常識‐最新の知識と治療の極意)

      Volume: 61 Pages: 793-799

    • Related Report
      2019 Annual Research Report
  • [Journal Article] アトピー性皮膚炎の臨床的特徴とサブタイプ Skin manifestations in subtypes of atopic dermatitis2019

    • Author(s)
      戸倉新樹
    • Journal Title

      皮膚アレルギーフロンティア

      Volume: 17 Pages: 15-20

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Decreased expression of suprabasin induces aberrant differentiation and apoptosis of epidermal keratinocytes: Possible role for atopic dermatitis2019

    • Author(s)
      Aoshima M, Phadungsaksawasdi P, Nakazawa S, Iwasaki M, Sakabe JI, Umayahara T, Yatagai T, Ikeya S, Shimauchi T, Tokura Y
    • Journal Title

      J Dermatol Sci

      Volume: 95 Issue: 3 Pages: 107-112

    • DOI

      10.1016/j.jdermsci.2019.07.009

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An intuitive explanation of dermoscopic structures by digitally reconstructed pathological horizontal top-down view images2019

    • Author(s)
      Kasuya A, Aoshima M, Fukuchi K, Shimauchi T, Fujiyama T, Tokura Y
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1

    • DOI

      10.1038/s41598-019-56522-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significance of IL-17A-producing CD8+CD103+ skin resident memory T cells in psoriasis lesion and their possible relationship to clinical course2019

    • Author(s)
      Kurihara K, Fujiyama T, Phadungsaksawasdi P, Ito T, Tokura Y
    • Journal Title

      J Dermatol Sci

      Volume: 95 Issue: 1 Pages: 21-27

    • DOI

      10.1016/j.jdermsci.2019.06.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Vitamin D3 analogue calcipotriol suppresses CpG-activated TLR9-MyD88 signalling in murine plasmacytoid dendritic cells.2018

    • Author(s)
      Suzuki T, Sakabe J, Kamiya K, Funakoshi A, Tokura Y.
    • Journal Title

      Clin Exp Dermatol

      Volume: 43 Issue: 4 Pages: 445-448

    • DOI

      10.1111/ced.13397

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] M2 macrophages promote wound-induced hair neogenesis.2018

    • Author(s)
      Kasuya A, Ito T, Tokura Y.
    • Journal Title

      J Dermatol Sci

      Volume: 91 Issue: 3 Pages: 250-255

    • DOI

      10.1016/j.jdermsci.2018.05.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of plasmablasts by follicular helper T cell-CXCL13 axis upon occurrence of herpes zoster.2018

    • Author(s)
      Fukuchi K, Shimauchi T, Tatsuno K, Tokura Y.
    • Journal Title

      Clin Immunol

      Volume: 195 Pages: 93-100

    • DOI

      10.1016/j.clim.2018.08.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensitive skin is highly frequent in extrinsic atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier impairment.2018

    • Author(s)
      Yatagai T, Shimauchi T, Yamaguchi H, Sakabe J-I, Aoshima M, Ikeya S, Tatsuno K, Fujiyama T, Ito T, Ojima T, Tokura Y:
    • Journal Title

      J Dermatol Sci

      Volume: 89 Issue: 1 Pages: 33-39

    • DOI

      10.1016/j.jdermsci.2017.10.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study.2017

    • Author(s)
      Saeki H, Kabashima K, Tokura Y, Murata Y, Shiraishi A, Tamamura R, Randazzo B, Imanaka K:
    • Journal Title

      Br J Dermatol

      Volume: 177 Issue: 2 Pages: 419-427

    • DOI

      10.1111/bjd.15493

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intrinsic atopic dermatitis shows high serum nickel concentration2015

    • Author(s)
      Yamaguchi H, Hirasawa N, Asakawa S, Okita K, Tokura Y:
    • Journal Title

      Allergology International

      Volume: 64 Issue: 3 Pages: 282-284

    • DOI

      10.1016/j.alit.2015.01.003

    • NAID

      130005290273

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] The cutaneous barrier function in atopic eczema: Causes and consequences2019

    • Author(s)
      Tokura Y
    • Organizer
      24th World Congress of Dermatology Milano 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A potential role of galectin-7 as a stabilizer for IL-4/IL-13-induced barrier disruption in atopic dermatitis2019

    • Author(s)
      Shimauchi T, Umayahara T, Iwasaki M, Aoshima M, Nakazawa S, Tokura Y
    • Organizer
      Society for Investigative Dermatology 77th Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CD8+CD103+ skin resident memory T cells are a subpopulation of CD8+MDR-1+ cells in lesional skin of psoriasis and correlate with the clinical course.2018

    • Author(s)
      Kurihara K, Fujiyama T, Ito T, Tokura Y.
    • Organizer
      International Investigative Dermatology (IID2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Skin-Infiltrating Th17/Tc17 and Th1/Tc1cells are signficantly decreased and IL-17+ CD103+ resident memory T cells partly remain after secukinumab treatment.2018

    • Author(s)
      Fujiyama T, Umayahara T, Kurihara K, Shimauchi T, Ito T, Hashizume H, Yagi H, To.kura Y.
    • Organizer
      International Investigative Dermatology (IID2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] M2 macrophages promote wound-induced hair neogenesis through the production of growth factors.2018

    • Author(s)
      Kasuya A, Ito T, Tokura Y.
    • Organizer
      13th Meeting of the German-Japanese Society of Drematology (GJSD2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CD103陽性皮膚レジデントメモリーT細胞と乾癬の長期予後との関連性2018

    • Author(s)
      栗原和生,藤山俊晴,伊藤泰介,戸倉新樹.
    • Organizer
      第33回日本乾癬学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Secukinumab therapy significantly decreases skin-infiltrating Th17/Tc17 and Th1/Tc1 lymphocytes and moderately reduces IL-17+CD103+ skin resident memory T cells.2018

    • Author(s)
      Tokura Y, Fujiyama T, Umayahara T, Kurihara K, Shimauchi T, Ito T, Hashizume H, Yagi H
    • Organizer
      European Academy of Dermatology and Venereology 27th Annual Congress (EADV2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of skin-infiltrating MDR1-positive T cell on topical corticosteroid resistance in pspriasis.2018

    • Author(s)
      Fujiyama T, Kurihara K, Ito T, Hashizume H, Tokura Y.
    • Organizer
      European Academy of Dermatology and Venereology 27th Annual Congress (EADV2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sensitive skin is highly frequent in atopic dermatitis and correlates with disease severity markers but not necessarily with skin barrier assessments.2017

    • Author(s)
      Yatagai T, Shimauchi T, Yamaguchi H, Sakabe J, Aoshima M, Ikeya S, Tatsuno K, Fijiyama T, Ito T, Tokura Y:
    • Organizer
      Society for Investigative Dermatology 76th Annual Meetinng
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Galectin-7 is extrancellularly released from epidermal keratinocytes in atopic dermatitis and skin and from cultured kerationcytes by IL-4/IL-13.2017

    • Author(s)
      Umayahara T, Sakabe J, Aoshima M, Shimauchi T, Tokura Y
    • Organizer
      第66回日本アレルギー学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Extrinsic and Intrinsic Types of Atopic Dermatitis.2017

    • Author(s)
      Tokura Y:
    • Organizer
      The 1st CICM International Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] High serum and epidermal extracellular levels of galectin-7 in atopic dermatitis.2017

    • Author(s)
      Umayahara T, Aoshima M, Iwasaki M, Yatagai T, Sakabe J, Tokura Y, Shimauchi T:
    • Organizer
      47th Annual ESDR Meeting in 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Serum galectin-7 derived possibly from IL-4/IL-13 stimulated keratinocytes is a useful biomarker for barrier dysfunction in atopic dermatitis.2017

    • Author(s)
      Umayahara T, Aoshima M, Iwasaki M, Yatagai T, Sakabe J, Tokura Y, Shimauchi T:
    • Organizer
      The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Knockdown of Suprabasin in a three-dimensional Epidermal Model Inhibits Differentiation of Keratinocyte.2017

    • Author(s)
      Aoshima M, Nakazawa S, Umayahara T, Sakabe J, Yatagai T, Ikeya S, Shimauchi T, Tokura Y:
    • Organizer
      The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Book] エビデンスに基づくアトピー性皮膚炎性皮膚炎治療あたらしい潮流2019

    • Author(s)
      戸倉新樹
    • Total Pages
      256
    • Publisher
      中山書店
    • ISBN
      9784521747767
    • Related Report
      2019 Annual Research Report
  • [Book] ここが大事!高齢者皮膚診療のコツとピットフォール2019

    • Author(s)
      戸倉 新樹、秋山 真志
    • Total Pages
      222
    • Publisher
      南江堂
    • ISBN
      9784524249350
    • Related Report
      2019 Annual Research Report
  • [Book] 臨床力がアップする!皮膚免疫アレルギーハンドブック2018

    • Author(s)
      戸倉新樹.藤本学.椛島健治
    • Total Pages
      394
    • Publisher
      南江堂
    • ISBN
      9784524242764
    • Related Report
      2018 Annual Research Report
  • [Book] Evolution of Atopic Dermatitis in the 21st Century2018

    • Author(s)
      Tokura Y:
    • Total Pages
      381
    • Publisher
      Springer
    • ISBN
      9789811055409
    • Related Report
      2017 Annual Research Report
  • [Remarks] 浜松医科大学医学部皮膚科学講座ホームページ

    • URL

      http://www2.hama-med.ac.jp/w1b/derm/index.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

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