Role of lymphatic flaw in wound healing and tumor immunity

• Project/Area Number: 22791057
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: The 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: ¥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.

Research Products

• [Journal Article] Lymphatic dysfunction impairs antigen-specific immunization, but augments tissue swelling following contact with allergen (2012)
  • 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(3Pt1) Issue: 3 Pages: 667-676
  • DOI: 10.1038/jid.2011.349
  • Peer Reviewed
• [Journal Article] High levels of LIGHT and low levels of soluble HVEM in sera of patients with atopic dermatitis (2012)
  • 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: 181-182
  • DOI: 10.1111/j.1365-2230.2011.04079.x
  • Peer Reviewed
• [Journal Article] Low HVEM Expression on Dermal Fibroblasts Contributes to a Th2-dominant Microenvironment in Advanced Cutaneous T Cell Lymphoma (2012)
  • 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: 1280-1289
  • DOI: 10.1038/jid.2011.470
  • Peer Reviewed
• [Journal Article] IL-22, but not IL-17, dominant environment in cutaneous T cell lymphoma (2011)
  • 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(24) Issue: 24 Pages: 7529-7538
  • DOI: 10.1158/1078-0432.ccr-11-1192
  • Peer Reviewed
• [Journal Article] Blocking MAPK signaling downregulates CCL21 in lymphatic endothelial cells and impairs contact hypersensitivity responses (2011)
  • 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(9) Issue: 9 Pages: 1927-1935
  • DOI: 10.1038/jid.2011.135
  • 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 Res Volume: 71(6) Issue: 6 Pages: 2056-2065
  • DOI: 10.1158/0008-5472.can-10-3764
  • Peer Reviewed
• [Journal Article] Kaposi's sarcoma and human dermal microvascular endothelial cells infected with Kaposi's sarcoma-associated herpesvirus express CCL21 (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Differential patterns of CXCR3, CCR3, and CCR10 expression in mycosis fungoides, Sezary syndrome and CD30+ lymphoproliferative disorders : immunohistochemical study of 43 samples (2011)
  • 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: 142-144
  • DOI: 10.1016/j.jdermsci.2011.07.004
  • Peer Reviewed
• [Journal Article] Erythrodermic cutaneous T-cell lymphoma : How to differentiate this rare disease from atopic dermatitis (2011)
  • 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
  • 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
  • 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
  • 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: J Invest Dermatol Volume: 130(9) Issue: 9 Pages: 2304-2311
  • DOI: 10.1038/jid.2010.128
  • 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
  • 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
  • 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
  • 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
  • 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
  • Peer Reviewed
• [Presentation] Effect of cilostazol on lymphatic endothelial cells in vitro and lymph flow in vivo (2011)
  • 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
• [Presentation] Association of the numbers of CD163^+macrophages in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma (2011)
  • 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
• [Presentation] Association of the numbers of CD163^+ macrophages in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma (2011)
  • 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
• [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
• [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
• [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
• [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