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Phagocytosis of apoptotic cells and cross-presentation by DC

Research Project

Project/Area Number 22790451
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionTohoku University

Principal Investigator

NAKAYAMA Masafumi  東北大学, 加齢医学研究所, 助教 (20453582)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords樹状細胞 / NK細胞 / MHCクラスII / 抗原提示 / MHC class II / 細胞間膜輸送 / 貪食 / 死細胞
Research Abstract

N atural killer (NK)cells contribute to not only innate but also adaptive immunity by interacting with dendritic cells (DCs)and T cells. All activated human NK cells express HLA-DR and can initiate MHCII-dependent CD4^+ T cell proliferation ; however, the expression of MHCII by mouse NK cells and its functional significance are controversial. In this study, we show that NK-DC interactions result in the emergence of MHCII-positive NK cells. Upon in vitro or in vivo activation, mouse conventional NK cells did not induce MHCII transcripts, but rapidly acquired MHCII protein from DCs. MHCII H2-Ab1-deficient NK cells turned I-A b-positive when adoptively transferred into wild type (WT)mice or when cultured with WT splenic DCs. NK acquisition of MHCII was mediated by intercellular membrane transfer called trogocytosis, but not upon DAP10/12 and MHCI-binding NK cell receptor signaling. MHCII-dressed NK cells concurrently acquired cost imulatory molecules such as CD80 and CD86 from DCs ; however, their expression did not reach functional levels. Therefore, MHCII-dressed NK cells inhibited DC-induced CD4^+ T cell responses rather than activated CD4^+ T cells by competitive antigen presentat ion. In a mouse model for delayed-type hypersensitivity, adoptive transfer of MHCII-dressed NK cells attenuated the footpad swelling. These results suggest that MHCII-dressed NK cells generated through NK-DC interactions regulate T cell-mediated immune r esponses.

Report

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

    (21 results)

All 2011 2010 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (7 results) Book (1 results) Remarks (6 results)

  • [Journal Article] Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4^+ T cells2011

    • Author(s)
      Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, Ogasawara K
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 108 Pages: 18360-18365

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Importinβ1 protein-mediated nuclear localization of death receptor 5 (DR5)limits DR5/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death of human tumor cells2011

    • Author(s)
      Kojima Y, Nakayama M, Nishina T, Nakano H, Koyanagi M, Takeda K, Okumura K, Yagita H
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 43383-43393

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] IFN-g production by lung NK cells is critical for the natural esistance to pulmonary metastasis of B16 melanoma in mice2011

    • Author(s)
      Takeda K, Nakayama M, Sakaki M, hayakawa Y, Imawari M, Ogasawara K, Okumura K, Smyth MJ
    • Journal Title

      J Leukoc Biol

      Volume: 90 Pages: 777-785

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells2011

    • Author(s)
      Nakayama M., et al
    • Journal Title

      Proc.Natl.Acad.Sci.USA

      Volume: 108 Pages: 18360-18365

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Importin b1 protein-mediated nuclear localization of death receptor 5 (DR5) limits DR5/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death of human tumor cells2011

    • Author(s)
      Kojima Y., et al
    • Journal Title

      J.Biol.Chem.

      Volume: 286 Pages: 43383-43393

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IFN-g production by lung NK cells is critical for the natural resistance to pulmonary metastasis of B16 melanoma in mice2011

    • Author(s)
      Takeda K., et al
    • Journal Title

      J.Leukoc.Biol.

      Volume: 90 Pages: 777-785

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Timファミリー分子を介したアポトーシス細胞貪食機構2010

    • Author(s)
      中山勝文
    • Journal Title

      生物と化学(日本農芸化学会誌)

      Volume: 48 Pages: 806-808

    • Related Report
      2010 Annual Research Report
  • [Presentation] Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells2011

    • Author(s)
      Nakayama M, Takeda K, Kawano M, Takai T, Ishii N, Ogasawara K
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      千葉
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Investigation of metal allergy using muse model2011

    • Author(s)
      Kawano M, Kumagai K, Kobayashi H, Nakayama M, Suzuki R, Ogasawara K
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report
  • [Presentation] Importinβ1 protein-mediated nuclear localization of death receptor 5 (DR5)limits DR5/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death of human tumor cells2011

    • Author(s)
      Kojima Y, Nakayama M, Nishina T, Nakano H, Koyanagi M, Takeda K, Okumura K, Yagita H
    • Organizer
      13th International TNF conference
    • Place of Presentation
      Awaji, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] Investigation of metal allergy using mouse model2011

    • Author(s)
      Kawano M., et al
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      千葉
    • Related Report
      2011 Annual Research Report
  • [Presentation] Importin b1 protein-mediated nuclear localization of death receptor 5 (DR5) limits DR5/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced cell death of human tumor cells2011

    • Author(s)
      Kojima Y., et al
    • Organizer
      13^<th> International TNF conference
    • Place of Presentation
      Awaji, Japan
    • Related Report
      2011 Annual Research Report
  • [Presentation] Tim-3を介するCD8α^+DCの死細胞貪食およびクロスプレゼンテーション機構2010

    • Author(s)
      中山勝文, 他2名
    • Organizer
      第6回血液学若手研究者勉強会(麒麟塾)
    • Place of Presentation
      東京
    • Year and Date
      2010-06-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] Staphylococcus aureus binds to paired Ig-like receptor-B to suppress the innate immune responses2010

    • Author(s)
      Nakayama M, et al.
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2010 Annual Research Report
  • [Book] Janeway's免疫生物学 第7版(免疫学研究者のための道具箱 翻訳)2010

    • Author(s)
      垣生園子、中山勝文
    • Publisher
      南江堂
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.tohoku.ac.jp/japanese/2011/11/press20111104-01.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://news.mynavi.mech.news/2011/11/04/097/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.tohoku.ac.jp/japanese/2011/11/press20111104-01.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://release.nikkei.co.jp/detail.cfm?relID=295892&lindID=5

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://news.mynavi.jp/news/2011/11/04/097/index.html

    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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