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Stat3 activation in epidermal keratinocytes induces psoriasis-like lesions via activation and migration of Langerhans cells to skin draining lymph nodes.

Research Project

Project/Area Number 15K09769
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionKochi University

Principal Investigator

Nakajima Kimiko  高知大学, 教育研究部医療学系臨床医学部門, 准教授 (20403892)

Co-Investigator(Kenkyū-buntansha) 山本 真有子  高知大学, 教育研究部医療学系臨床医学部門, 助教 (20423478)
中島 英貴  高知大学, 教育研究部医療学系臨床医学部門, 講師 (70314995)
佐野 栄紀  高知大学, 教育研究部医療学系臨床医学部門, 教授 (80273621)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords乾癬 / 皮膚バリア障害 / Stat3 / Langerhans細胞 / バリア障害
Outline of Final Research Achievements

Langerhans cells (LCs) were activated in psoriatic lesion of patients with psoriasis and psoriasis-like lesions of K5.Stat3C mice treated with 12-O-tetradecanoylphorbol
-13-acetate (TPA). Notably, compared with nontransgenic mice, K5.Stat3C mice showed an increased number of LCs in the sDLNs before psoriasis-like lesions developed. Importantly, the psoriasis-like lesions in K5.Stat3C mice_langerin DTR KI mice were significantly attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesions. Flow cytometric analysis of cells from sDLNs in TPA treated-K5.Stat3C mice revealed that LCs produced IL-23. Moreover, IL-1α was up-regulated in keratinocytes of Stat3C mice. Our study suggests that Stat3 activation in keratinocytes induces the activation of LCs and that migration of LCs to sDLNs is essential for the pathogenesis of psoriasis through producing inflammatory cytokines such as IL-23.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Mouse models of psoriasis and their relevance2018

    • Author(s)
      Nakajima K, Sano S
    • Journal Title

      J Dermatol

      Volume: 45 Issue: 3 Pages: 252-263

    • DOI

      10.1111/1346-8138.14112

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel frame-shift mutation in SERPINB7 in a Japanese patient with Nagashima-type palmoplantar keratosis.2016

    • Author(s)
      Nakajima K, Ishiguro M, Shiohama A, Kubo A, Sano S.
    • Journal Title

      J Dermatol.

      Volume: - Issue: 7 Pages: 841-843

    • DOI

      10.1111/1346-8138.13556

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 乾癬とIL-12/23受容体.2015

    • Author(s)
      中島喜美子
    • Journal Title

      分子リウマチ治療

      Volume: 8 Pages: 219-223

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 全身作用型経皮吸収型製剤の進歩と皮膚トラブルについて2015

    • Author(s)
      中島喜美子
    • Journal Title

      皮膚病診療

      Volume: 37 Pages: 434-441

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 乾癬病態における「表皮と免疫系のクロストーク」2017

    • Author(s)
      中島喜美子
    • Organizer
      第116回日本皮膚科学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Barrier abnormality due to ceramide deficiency leads to psoriasi-form inflammation in a mouse model2017

    • Author(s)
      Nakajima K, Sano S
    • Organizer
      第32回日本乾癬学会学術大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Mouse model of psoriasis and their relevance.2017

    • Author(s)
      Nakajima K
    • Organizer
      The 42nd Annual Meeting of the Japanese Society for Investigative Dermatology2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Langerhans cells are essential for the development of psoriasis-like lesions in a mouse model2016

    • Author(s)
      Kimiko Nakajima, Sayo Kataoka, Mayuko Yamamoto, Bernard Malissen, Shigetoshi Sano
    • Organizer
      第45回日本免疫学会学術集会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] モデルマウスを用いた乾癬病態の解明2016

    • Author(s)
      中島喜美子
    • Organizer
      第31回日本乾癬学会学術大会
    • Place of Presentation
      ホテル東日本宇都宮(栃木県宇都宮市)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 乾癬の病態におけるランゲルハンス細胞の役割2016

    • Author(s)
      中島喜美子、片岡佐誉、山本真有子、Bernard Malisse、佐野栄紀
    • Organizer
      第31回日本乾癬学会学術大会
    • Place of Presentation
      ホテル東日本宇都宮(栃木県宇都宮市)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] モデルマウスを用いた乾癬病態の解明2016

    • Author(s)
      中島喜美子
    • Organizer
      第115回日本皮膚科学会総会
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Year and Date
      2016-06-02
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Langerhans cells migrate to lymph nodes with increased number in mice with Stat3 activation in epidermal keratinocytes and are essential for development of psoriasis-like lesions2015

    • Author(s)
      Kimiko Nakajima, Sayo Kataoka, Mayuko Yamamoto, Bernard Malissen, Shigetoshi Sano
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(札幌)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Langerhans cells migrate to lymph nodes with increased number in mice with Stat3 activation in epidermal keratinocytes and are essential for development of psoriasis-like lesions2015

    • Author(s)
      Kimiko Nakajima, Sayo Kataoka, Mayuko Yamamoto, Bernard Malissen, Shigetoshi Sano
    • Organizer
      14th International Langerhans cell Workshop
    • Place of Presentation
      Kyoto International Community House (京都)
    • Year and Date
      2015-11-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Langerhans cells migrate to lymph nodes with increased number in mice with Stat3 activation in epidermal keratinocytes and are essential for development of psoriasis-like lesions2015

    • Author(s)
      Kimiko Nakajima, Sayo Kataoka, Mayuko Yamamoto, Bernard Malissen, Shigetoshi Sano
    • Organizer
      45th European Society for Dermatological Research
    • Place of Presentation
      The Beurs-World Trade Center (ロッテルダム)
    • Year and Date
      2015-09-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 乾癬病態におけるランゲルハンス細胞の役割2015

    • Author(s)
      中島喜美子, 片岡佐誉, 山本真有子, Bernard Malissen, 佐野栄紀
    • Organizer
      第30回日本乾癬学会
    • Place of Presentation
      ウェスティンナゴヤキャッスル(名古屋)
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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