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Defining the Langerhans cell niche and the anchoring point

Research Project

Project/Area Number 21689032
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionKeio University

Principal Investigator

NAGAO Keisuke  慶應義塾大学, 医学部, 講師 (40286521)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥27,430,000 (Direct Cost: ¥21,100,000、Indirect Cost: ¥6,330,000)
Fiscal Year 2011: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2010: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2009: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Keywordsランゲルハンス細胞 / 毛嚢 / ケモカイン / タイトジャンクション / 樹状細胞 / ラングルハンス細胞 / 前駆細胞
Research Abstract

Langerhans cells(LC) are epidermal dendritic cells with incompletely understood origins that associate with hair follicles(HF) for unknown reasons. In this work, we showed that mouse HFs recruited Gr-1high monocyte-derived LC precursors(pre-LCs), whose epidermal entry was CCR2/6 dependent, whereas CCR8 inhibited LC recruitment. Distinct HF regions differentially expressed CCR2/6 ligands. The isthmus expressed CCL2, the infundibulum expressed CCL20, and keratinocytes in the bulge produced the CCR8 ligand, CCL8. Thus, distinct HF keratinocyte subpopulations promote or inhibit LC repopulation via differential chemokine production, a feature also demonstrated in humans. LCs/Pre-LCs failed to enter hairless skin in both mice and humans, establishing HFs as LC portals, a new paradigm in leukocyte trafficking and regulation of skin inflammation(Nat Immunol, in press). To prove the above findings, we generated and characterized TACE/Sox9 mice, which develop progressive alopecia, and have reported mechanisms of hair loss as an independent manuscript(Stem Cells, in press). Furthermore, during this series of work, we functionally characterized LCs. We showed that LCs extend their dendrites through epidermal tight junctions to uptake skin surface bacteria-derived toxin to induce neutralizing antibodies that protected mice from experimental staphylococcal scalded skin syndrome(Ouchi et al. J Exp Med 2011).

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (16 results)

All 2012 2011 2009

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (11 results)

  • [Journal Article] Stress-induced chemokine production by hair follicles regulate dendritic cell trafficking in skin2012

    • Author(s)
      Keisuke Nagao, Tetsuro Kobayashi, Kazuyo Moro, Manabu Ohyama, Takeya Adachi, Daniela Y. Kitashima, Satoshi Ueha, Keisuke Horiuchi, Hideaki Tanizaki, Kenji Kabashima, Akiharu Kubo, Young-hun Cho, Bjorn E. Clausen, Kouji Matsushima, Makoto Suematsu, Glaucia C. Furtado, Sergio A. Lira, Joshua M. Farber, Mark C. Udey, and Masayuki Amagai
    • Journal Title

      Nature Immunology

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Requirement of TACE/ADAM17 for hair follicle bugle niche establishment2012

    • Author(s)
      Keisuke Nagao, Tetsuro Kobayashi, Manabu Ohyama, Haruhiko Akiyama, Keisuke Horiuchi, Masayuki Amagai
    • Journal Title

      Stem Cells

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome2011

    • Author(s)
      Takeshi Ouchi, Akiharu Kubo, Mariko Yokouchi, Takeya Adachi, Tetsuro Kobayashi, Daniela Y. Kitashima, Hideki Fujii, Bjorn E. Clausen, Shigeo Koyasu, Masayuki Amagai, and Keisuke Nagao
    • Journal Title

      The Journal of Experimental Medicine

      Volume: 208(22143886) Pages: 2607-2613

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome2011

    • Author(s)
      Ouchi T
    • Journal Title

      J Exp Med

      Volume: 208 Pages: 2607-2613

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers.2009

    • Author(s)
      Kubo A, et al.
    • Journal Title

      J Exp.Med. 206

      Pages: 2937-2946

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Requirement of TACE/ADAM17 for the maintenance of hair follicle stem cell niche2012

    • Author(s)
      Tetsuro Kobayashi, Keisuke Horiuchi, Masayuki Amagai, Keisuke Nagao
    • Organizer
      75^<th> Annual Meeting for Society for Investigative Dermatology
    • Place of Presentation
      Raleigh, NC, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Dendritic cell trafficking in skin is regulated by hair follicles via chemokine production2012

    • Author(s)
      Keisuke Nagao, Tetsuro Kobayashi, Kazuyo Moro, Kenji Kabashima, Manabu Ohyama, Young-hun Cho, Bjorn E. Clausen, Mark C. Udey, and Masayuki Amagai
    • Organizer
      75^<th> Annual Meeting for Society for Investigative Dermatology
    • Place of Presentation
      Raleigh, NC, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Antigen capture through tight junctions by Langerhans cells confer pre-emptive immunity in experimental staphylococcal scalded skin syndrome2011

    • Author(s)
      Nagao K
    • Organizer
      第36回日本研究皮膚科学会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2011-12-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] Langerhans cells confer pre-emptive immunity via antigen capture through tight junctions in experimental staphylococcal scalded skin syndrome2011

    • Author(s)
      永尾圭介
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Regulation of dendritic cell trafficking by hair follicles2011

    • Author(s)
      Nagao K
    • Organizer
      12th International Workshop on Langerhans cells
    • Place of Presentation
      オーストリア(インスブルック)(招待講演)
    • Year and Date
      2011-11-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] 経皮免疫におけるランゲルハンス細胞の役割2011

    • Author(s)
      永尾圭介
    • Organizer
      第39回日本臨床免疫学会総会
    • Place of Presentation
      京王プラザホテル(東京都)(招待講演)
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Langerhans cells play an essential role in inducing protective humoral immune response subsequent to antigen uptake through tight junctions2011

    • Author(s)
      Ouchi T
    • Organizer
      European Society of Dermatological Research
    • Place of Presentation
      スペイン(バルセロナ)
    • Year and Date
      2011-09-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] 毛嚢による皮膚樹状細胞トラフィッキングの制御2011

    • Author(s)
      永尾圭介
    • Organizer
      第32回日本炎症・再生医学会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2011-06-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Langerhans cells play an essential role in inducing protective humoral immune response subsequent to antigen uptake through tight junctions2011

    • Author(s)
      Takeshi Ouchi, Akiharu Kubo, Takeya Adachi, Tetsuro Kobayashi, Daniela Y. Kitashima, Hideki Fujii, Bjoern E. Clausen, Shigeo Koyasu, Masayuki Amagai, and Keisuke Nagao
    • Organizer
      41th Annual ESDR meeting
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2011 Final Research Report
  • [Presentation] Hair follicles regulate dendritic cell trafficking in skin2011

    • Author(s)
      Keisuke Nagao
    • Organizer
      Cutting edge immunology and its clinical applications
    • Place of Presentation
      Netherlands
    • Related Report
      2011 Final Research Report
  • [Presentation] Bowen病における中心体制御異常の検討2009

    • Author(s)
      久保亮治
    • Organizer
      第108回日本皮膚科学会総会
    • Place of Presentation
      福岡
    • Year and Date
      2009-04-24
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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