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Role of lymphatic flaw in wound healing and tumor immunity

Research Project

Project/Area Number 22791057
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionThe University of Tokyo

Principal Investigator

SUGAYA Makoto  東京大学, 医学部附属病院, 講師 (90334408)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords免疫 / リンパ / 創傷治癒 / 腫瘍免疫
Research Abstract

Wound healing was significantly delayed in the transgenic(TG) mice with severe lymphatic dysfunction when compared to wild-type(WT) mice. In wounded skin of TG mice, mast cell numbers were increased, whereas macrophage numbers were decreased. Moreover, increased IL-10 mRNA levels and decreased levels of basic fibroblast growth factor were detected in wounded skin of TG mice compared to WT mice. Similar results were obtained using a different lymphedema model, in which circumferential full thickness skin excision was performed on the tails of WT mice to remove the superficial lymphatics. With regards to tumor immunity, TG mice that had been subcutaneously injected with B16 melanoma cells did not show metastasis in the draining lymph node(LN). Expression levels of TNF-. and IFN-. were significantly lower in the draining LN of TG mice compared to WT mice. By contrast, larger tumor formation was observed in the injected site in TG mice, suggesting that sufficient immune response against tumor cells was not established in the draining LN of TG mice.

Report

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

    (24 results)

All 2012 2011 2010

All Journal Article (17 results) (of which Peer Reviewed: 17 results) Presentation (7 results)

  • [Journal Article] Lymphatic dysfunction impairs antigen-specific immunization, but augments tissue swelling following contact with allergens2012

    • Author(s)
      Sugaya M, Kuwano Y, Suga H, Miyagaki T, Ohmatsu H, Kadono T, Okochi H, Blauvelt A, Tamaki K, Sato S.
    • Journal Title

      J Invest Dermatol

      Volume: 132 Issue: 3 PART 1 Pages: 667

    • DOI

      10.1038/jid.2011.349

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] High levels of LIGHT and low levels of soluble herpesvirus entry mediator in sera of patients with atopic dermatitis2012

    • Author(s)
      Morimura S, Sugaya M, Kai H, Kato T, Miyagaki T, Ohmatsu H, Kagami S, Asano Y, Mitsui H, Tada Y, Kadono T, Sato S
    • Journal Title

      Clinical and Experimental Dermatology

      Volume: 37 Issue: 2 Pages: 181

    • DOI

      10.1111/j.1365-2230.2011.04079.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low herpesvirus entry mediator (HVEM) expression on dermal fibroblasts contributes to a Th2-dominant microenvironment in advanced cutaneous T-cell lymphoma2012

    • Author(s)
      Miyagaki T, Sugaya M, Suga H, Morimura S, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 132 Issue: 4 Pages: 1280

    • DOI

      10.1038/jid.2011.470

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-22, but not IL-17, Dominant environment in cutaneous T-cell lymphoma2011

    • Author(s)
      Miyagaki T, Sugaya M, Suga H, Kamata M, Ohmatsu H, Fujita H, Asano Y, Tada Y, KadonoT, Sato S.
    • Journal Title

      Clin Cancer Res

      Volume: 17 Issue: 24 Pages: 7529

    • DOI

      10.1158/1078-0432.ccr-11-1192

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blocking MAPK signaling downregulates CCL21 in lymphatic endothelial cells and impairs contact hypersensitivity responses2011

    • Author(s)
      Miyagaki T, Sugaya M, Okochi H, Asano Y, Tada Y, Kadono T, Blauvelt A, Tamaki K, Sato S.
    • Journal Title

      Invest Dermatol

      Volume: 131 Issue: 9 Pages: 1927

    • DOI

      10.1038/jid.2011.135

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] CCL11-CCR3 interactions promote survival of anaplastic large cell lymphoma cells via ERK1/2 activation2011

    • Author(s)
      Miyagaki T, Sugaya M, Murakami T, Asano Y, Tada Y, Kadono T, Okochi H, Tamaki K, Sato S.
    • Journal Title

      Cancer Res

      Volume: 71 Issue: 6 Pages: 2056

    • DOI

      10.1158/0008-5472.can-10-3764

    • URL

      https://pure.teikyo.jp/en/publications/05a734c3-5da0-49ca-8cf7-7aa37e161092

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Kaposi's sarcoma and human dermal microvascular endothelial cells infected with Kaposi's sarcoma-associated herpesvirus express CCL212011

    • Author(s)
      Sugaya M, Reed S, Rose PP, de la Motte S, Raggo CM, Kurtz SE, Moses AV, Fruh K, Blauvelt A.
    • Journal Title

      Dermatol Sci

      Volume: 61(2) Issue: 2 Pages: 139-142

    • DOI

      10.1016/j.jdermsci.2010.11.017

    • NAID

      10030890204

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential patterns of CXCR3, CCR3, and CCR10 expression in mycosis fungoides, Sezary syndrome and CD30 <sup>+</sup> lymphoproliferative disorders: Immunohistochemical study of 43 samples2011

    • Author(s)
      Suga H, Sugaya M, Miyagaki T, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S
    • Journal Title

      Journal of Dermatological Science

      Volume: 64 Issue: 2 Pages: 142

    • DOI

      10.1016/j.jdermsci.2011.07.004

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Erythrodermic cutaneous T-cell lymphoma : How to differentiate this rare disease from atopic dermatitis2011

    • Author(s)
      Miyagaki T, Sugaya M
    • Journal Title

      Journal of Dermatological Science

      Volume: 64 Issue: 1 Pages: 1-6

    • DOI

      10.1016/j.jdermsci.2011.07.007

    • NAID

      10030892625

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High levels of soluble ST2 and low levels of IL-33 in sera of patients with HIV infection.2011

    • Author(s)
      Miyagaki T, Sugaya M, Yokobayashi H, Kato T, Ohmatsu H, Fujita H, Saeki H, Kikuchi Y, Tamaki T, Sato S
    • Journal Title

      Journl of Investigative Dermatology

      Volume: 131 Pages: 794-796

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CCL11-CCR3 interactions promote survival of anaplastic large cell lymphoma cells via ERK1/2 activation.2011

    • Author(s)
      Miyagaki T, Sugaya M, Murakami T, Asano Y, Tada Y, Kadono T, Okochi H, Tamaki K, Sato S
    • Journal Title

      Cancer Research

      Volume: 71 Pages: 2056-2065

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eotaxins and CCR3 interaction regulates Th2 environment of cutaneous T cell lymphoma2010

    • Author(s)
      Miyagaki T, Sugaya M, Fujita H, Ohmatsu H, Kakinuma T, Kadono T, Tamaki K, Sato S.
    • Journal Title

      J Invest Dermatol

      Volume: 130(9) Issue: 9 Pages: 2304-2311

    • DOI

      10.1038/jid.2010.128

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemokines and cutaneous lymphoma.2010

    • Author(s)
      Sugaya M
    • Journal Title

      Journal of Dermatological Science

      Volume: 59 Pages: 81-89

    • NAID

      10027401703

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eotaxins and CCR3 interaction regulates Th2 environment of cutaneous T cell lymphoma.2010

    • Author(s)
      Miyagaki T, Sugaya M, Fujita H, Ohmatsu H, Kakinuma T, Kadono T, Tamaki K, Sato S
    • Journal Title

      Journl of Investigative Dermatology

      Volume: 130 Pages: 2304-2311

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a novel marker for dendritic cell maturation, mouse transmembrane protein 123.2010

    • Author(s)
      Takekoshi T, Tada Y, Watanabe T, Sugaya M, Hoashi T, Komine M, Kawashima T, Shimizu T, Hau CS, Asahina A, Yokomizo T, Sato S, Tamaki K
    • Journal Title

      Journal of Biological Chemistry

      Volume: 285 Pages: 31876-31884

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] α4β7 integrin is essential for contact hypersensitivity by regulating migration of T cells to skin.2010

    • Author(s)
      Ohmatsu H, Kadono T, Sugaya M, Tomita M, Kai H, Miyagaki T, Saeki H, Tamaki K, Steeber DA, Tedder TF, Sato S
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 126 Pages: 1267-1276

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kaposi's sarcoma and human dermal microvascular endothelial cells infected with Kaposi's sarcoma-associated herpesvirus express CCL21.2010

    • Author(s)
      Sugaya M, Reed S, Rose PP, de la Motte S, Raggo CM, Kurtz SE, Moses AV, Fruh K, Blauvelt A
    • Journal Title

      Journal of Dermatological Science

      Volume: 61 Pages: 139-142

    • NAID

      10030890204

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Effect of cilostazol on lymphatic endothelial cells in vitro and lymph flow in vivo2011

    • Author(s)
      Kimura T, Hamazaki T, Sugaya M, Sato S, Okochi H
    • Organizer
      36th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Association of the numbers of CD163^+macrophages in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma2011

    • Author(s)
      Sugaya M, Miyagaki T, Ohmatsu H, Suga H, Kai H, Kamata M, Tada Y, Sato S
    • Organizer
      The 71^<st> Annual Meeting of the Society for Investigative Dermatology
    • Place of Presentation
      アメリカ合衆国フェニックス
    • Related Report
      2011 Final Research Report
  • [Presentation] Association of the numbers of CD163^+ macrophages in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma2011

    • Author(s)
      Sugaya M, Miyagaki T, Ohmatsu H, Suga H, Kai H, Kamata M, Tada Y, Sato S
    • Organizer
      The 71^<st> Annual Meeting of the Society for Investigative Dermatology
    • Place of Presentation
      アメリカ合衆国フェニックス
    • Related Report
      2011 Annual Research Report
  • [Presentation] Differential patterns of CXCR3, CCR3, and CCR10 expression in mycosis fungoides, Sezary syndrome, and CD30+lymphoproliferative disorders2010

    • Author(s)
      Sugaya M, Suga H, Miyagaki T, Ohmatsu H, Sato S
    • Organizer
      First World Congress of Cutaneous Lymphomas
    • Place of Presentation
      アメリカ合衆国シカゴ
    • Related Report
      2011 Final Research Report
  • [Presentation] Eotaxin-CCR3 interaction increases survival of anaplastic large cell lymphoma cells via ERK1/2 activation pathway(oral presentation in Cutaneous T Cell Lymphoma Symposium)2010

    • Author(s)
      Miyagaki T, Sugaya M, Kadono T, Murakami T, Okochi H, Tamaki K, Sato S
    • Organizer
      The 70^<th> annual meeting of Society for Investigative Dermatology
    • Place of Presentation
      アメリカ合衆国アトランタ
    • Related Report
      2011 Final Research Report
  • [Presentation] Eotaxin-CCR3 interaction increases survival of anaplastic large cell lymphoma cells via ERK1/2 activation pathway (oral presentation in Cutaneous T Cell Lymphoma Symposium).2010

    • Author(s)
      Miyagaki T, Sugaya M, Kadono T, Murakami T, Okochi H, Tamaki K, Sato S
    • Organizer
      The 70^<th> annual meeting of Society for Investigative Dermatology.
    • Place of Presentation
      アメリカ合衆国アトランタ
    • Related Report
      2010 Annual Research Report
  • [Presentation] Differential patterns of CXCR3, CCR3, and CCR10 expression in mycosis fungoides, Sezary syndrome, and CD30+ lymphoproliferative disorders.2010

    • Author(s)
      Sugaya M, Suga H, Miyagaki T, Ohmatsu H, Sato S
    • Organizer
      First World Congress of Cutaneous Lymphomas.
    • Place of Presentation
      アメリカ合衆国シカゴ
    • Related Report
      2010 Annual Research Report

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

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