Function of lymphatics in tumor immunity, vasculitis, and imiquimod-induced psoriasis-like dermatitis

• Project/Area Number: 24591623
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: SUGAYA Makoto 東京大学, 医学部附属病院, 准教授 (90334408)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: リンパ / 腫瘍免疫 / リンパ節 / CD8陽性細胞 / アルサス反応 / Fcγ受容体 / 血管炎 / 免疫

Outline of Final Research Achievements

Primary tumor growth was augmented in lymphedematous mice when B16 melanoma cells were subcutaneously injected. Expression of inflammatory cytokines as well as tumor-associated antigens in draining lymph nodes was significantly reduced in lymphedematous mice compared to wild-type mice. CD8+ T cells in draining LNs derived from lymphedematous mice bearing B16 melanoma also showed significantly decreased cytotoxic activity in vitro and in vivo. In summary, these findings suggest that lymphatic transport is essential in generating optimal tumor-specific immune responses. Moreover, early phase of leukocytoclastic vasculitis, the cutaneous and peritoneal reverse Arthus reactions, was attenuated in lymphedematous mice. Decreased Fc gamma receptor III expression on mast cells and macrophages may have resulted in reduced inflammation.

Research Products

• [Journal Article] TARC and I-TAC are sensitive markers reflecting pruritus in atopic dermatitis. (2014)
  • Author(s): Kimura T, Sugaya M, Suga H, Morimura S, Kai H, Kagami S, Yanaba K, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Acta Derm Venereol Volume: 94 Issue: 3 Pages: 331-2
  • DOI: 10.2340/00015555-1709
  • Peer Reviewed
• [Journal Article] TOX expression in different subtypes of cutaneous lymphoma. (2014)
  • Author(s): Morimura S, Sugaya M, Suga H, Miyagaki T, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Arch Dermatol Res Volume: 306 Issue: 9 Pages: 843-9
  • DOI: 10.1007/s00403-014-1501-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Skin barrier dysfunction and low antimicrobial peptide expression in cutaneous T-cell lymphoma. (2014)
  • Author(s): Suga H, Sugaya M, Miyagaki T, Ohmatsu H, Kawaguchi M, Takahashi N, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Clin Cancer Res Volume: 20 Issue: 16 Pages: 4339-48
  • DOI: 10.1158/1078-0432.ccr-14-0077
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cilostazol improves lymphatic function by inducing proliferation and stabilization of lymphatic endothelial cells. (2014)
  • Author(s): Kimura T, Hamazaki TS, Sugaya M, Fukuda S, Chan T, Tamura-Nakano M, Sato S, Okochi H.
  • Journal Title: J Dermatol Sci Volume: 74 Issue: 2 Pages: 150-8
  • DOI: 10.1016/j.jdermsci.2014.01.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The role of IL-32 in cutaneous T-cell lymphoma. (2014)
  • Author(s): Suga H, Sugaya M, Miyagaki T, Kawaguchi M, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: J Invest Dermatol Volume: 134 Issue: 5 Pages: 1428-35
  • DOI: 10.1038/jid.2013.488
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Serum levels of angiopoietin-2, but not angiopoietin-1, are elevated in patients with erythrodermic cutaneous T-cell lymphoma. (2014)
  • Author(s): Kawaguchi M, Sugaya M, Suga H, Miyagaki T, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Acta Derm Venereol Volume: 94 Issue: 1 Pages: 9-13
  • DOI: 10.2340/00015555-1633
  • Peer Reviewed
• [Journal Article] TLR4, rather than TLR2, regulates wound healing through TGF-β and CCL5 expression. (2014)
  • Author(s): Suga H, Sugaya M, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: J Dermatol Sci Volume: 73 Issue: 2 Pages: 117-24
  • DOI: 10.1016/j.jdermsci.2013.10.009
  • Peer Reviewed
• [Journal Article] Depsipeptide and roxithromycin induce apoptosis of lymphoma cells by blocking extracellular signal-regulated kinase activation. (2014)
  • Author(s): Morimura S, Sugaya M, Kai H, Miyagaki T, Asano Y, Tada Y, Kadono T, Murakami T, Sato S.
  • Journal Title: J Dermatol Volume: 41 Issue: 1 Pages: 57-62
  • DOI: 10.1111/1346-8138.12351
  • Peer Reviewed
• [Journal Article] Serum-soluble herpes virus entry mediator levels reflect disease severity and Th2 environment in cutaneous T-cell lymphoma. (2013)
  • Author(s): Miyagaki T, Sugaya M, Suga H, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Acta Derm Venereol Volume: 93 Issue: 4 Pages: 465-7
  • DOI: 10.2340/00015555-1523
  • Peer Reviewed
• [Journal Article] Serum gastrin-releasing peptide levels correlate with pruritus in patients with atopic dermatitis. (2013)
  • Author(s): Kagami S, Sugaya M, Suga H, Morimura S, Kai H, Ohmatsu H, Fujita H, Tsunemi Y, Sato S.
  • Journal Title: J Invest Dermatol Volume: 133 Issue: 6 Pages: 1673-5
  • DOI: 10.1038/jid.2013.38
  • Peer Reviewed
• [Journal Article] Interaction between CX3CL1 and CX3CR1 regulates vasculitis induced by immune complex deposition. (2013)
  • Author(s): Morimura S, Sugaya M, Sato S.
  • Journal Title: Am J Pathol Volume: 182 Issue: 5 Pages: 1640-7
  • DOI: 10.1016/j.ajpath.2013.01.023
  • Peer Reviewed
• [Journal Article] Delayed wound healing due to increased interleukin-10 expression in mice with lymphatic dysfunction. (2013)
  • Author(s): Kimura T, Sugaya M, Blauvelt A, Okochi H, Sato S.
  • Journal Title: J Leukoc Biol Volume: 94 Issue: 1 Pages: 137-45
  • DOI: 10.1189/jlb.0812408
  • Peer Reviewed
• [Journal Article] CXCR3 deficiency prolongs Th1-type contact hypersensitivity. (2013)
  • Author(s): Suga H, Sugaya M, Miyagaki T, Ohmatsu H, Okochi H, Sato S.
  • Journal Title: J Immunol Volume: 190 Issue: 12 Pages: 6059-70
  • DOI: 10.4049/jimmunol.1201606
  • Peer Reviewed
• [Journal Article] Serum visfatin levels in patients with atopic dermatitis and cutaneous T-cell lymphoma. (2013)
  • Author(s): Suga H, Sugaya M, Miyagaki T, Kawaguchi M, Morimura S, Kai H, Kagami S, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Eur J Dermatol Volume: 23 Issue: 5 Pages: 629-35
  • DOI: 10.1684/ejd.2013.2107
  • Peer Reviewed
• [Journal Article] Increased CCL18 expression in patients with cutaneous T-cell lymphoma: association with disease severity and prognosis. (2013)
  • Author(s): Miyagaki T, Sugaya M, Suga H, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: J Eur Acad Dermatol Venereol Volume: 27 Issue: 1
  • DOI: 10.1111/j.1468-3083.2012.04495.x
  • Peer Reviewed
• [Journal Article] Analysis of serum chemokine levels in patients with HIV-associated eosinophilic folliculitis. (2013)
  • Author(s): Yokobayashi H, Sugaya M, Miyagaki T, Kai H, Suga H, Yamada D, Minatani Y, Watanabe K, Kikuchi Y, Tamaki T, Sato S.
  • Journal Title: J Eur Acad Dermatol Venereol Volume: 27 Issue: 2 Pages: 212-216
  • DOI: 10.1111/j.1468-3083.2012.04592.x
  • Peer Reviewed
• [Journal Article] Association of Nerve Growth Factor, Chemokine (C-C motif) Ligands and Immunoglobulin E with Pruritus in Cutaneous T-cell Lymphoma. (2013)
  • Author(s): Suga H, Sugaya M, Miyagaki T, Ohmatsu H, Fujita H, Kagami S, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Acta Derm Venereol Volume: 93 Issue: 2 Pages: 144-9
  • DOI: 10.2340/00015555-1428
  • Peer Reviewed
• [Journal Article] Serum angiogenin levels are decreased in patients with psoriasis. (2012)
  • Author(s): Miyagaki T, Sugaya M, Kamata M, Suga H, Morimura S, Tatsuta A, Uwajima Y, Yamamoto M, Shibata S, Fujita H, Asano Y, Kadono T, Sato S, Tada Y.
  • Journal Title: Clin Exp Dermatol Volume: 37 Issue: 7 Pages: 792-3
  • DOI: 10.1111/j.1365-2230.2012.04345.x
  • Peer Reviewed
• [Journal Article] Serum IL-31 levels are increased in patients with cutaneous T-cell lymphoma. (2012)
  • Author(s): Ohmatsu H, Sugaya M, Suga H, Morimura S, Miyagaki T, Kai H, Kagami S, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Acta Derm Venereol Volume: 92 Issue: 3 Pages: 282-3
  • DOI: 10.2340/00015555-1345
  • Peer Reviewed
• [Journal Article] BAFF levels are increased in lesional skin and sera in patients with cutaneous T-cell lymphoma. (2012)
  • Author(s): Ohmatsu H, Sugaya M, Miyagaki T, Suga H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Br J Dermatol Volume: 167 Issue: 2 Pages: 359-67
  • DOI: 10.1111/j.1365-2133.2012.10998.x
  • Peer Reviewed
• [Journal Article] Angiogenin levels are increased in lesional skin and sera in patients with erythrodermic cutaneous T cell lymphoma. (2012)
  • Author(s): Miyagaki T, Sugaya M, Suga H, Akamata K, Ohmatsu H, Fujita H, Asano Y, Tada Y, Kadono T, Sato S.
  • Journal Title: Arch Dermatol Res Volume: 304 Issue: 5 Pages: 401-6
  • DOI: 10.1007/s00403-012-1238-0
  • Peer Reviewed
• [Journal Article] Association of the numbers of CD163(+) cells in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma. (2012)
  • Author(s): Sugaya M, Miyagaki T, Ohmatsu H, Suga H, Kai H, Kamata M, Fujita H, Asano Y, Tada Y, Kadono T, Okochi H, Sato S.
  • Journal Title: J Dermatol Sci Volume: 68 Issue: 1 Pages: 45-51
  • DOI: 10.1016/j.jdermsci.2012.07.007
  • Peer Reviewed
• [Presentation] リンパ流障害と皮膚免疫 (2015)
  • Author(s): 菅谷 誠
  • Organizer: 第39回日本リンパ学会総会
  • Place of Presentation: ソラシティカンファレンスセンター
  • Year and Date: 2015-03-27 – 2015-03-28
  • Invited
• [Presentation] Skin barrier dysfunction and relatively low antimicrobial peptide expression in cutaneous T-cell lymphoma (2014)
  • Author(s): Hiraku Suga, Makoto Sugaya, Tomomitsu Miyagaki, Hanako Ohmatsu, Makiko Kawaguchi, Naomi Takahashi, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato
  • Organizer: SID 73rd Annual Meeting
  • Place of Presentation: Albuquerque, New Mexico
  • Year and Date: 2014-05-07 – 2014-05-10
• [Presentation] Periostin contributes to a Th2-dominant environment of cutaneous T-cell lymphoma via thymic stromal lymphopoietin expression (2014)
  • Author(s): Naomi Takahashi, Makoto Sugaya, Hiraku Suga, Tomomitsu Miyagaki, Hanako Ohmatsu, Makiko Kawaguchi, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato
  • Organizer: SID 73rd Annual Meeting
  • Place of Presentation: Albuquerque, New Mexico
  • Year and Date: 2014-05-07 – 2014-05-10
• [Presentation] CXCR3 deficiency prolongs Th1-type contact hypersensitivity (2013)
  • Author(s): 菅谷 誠、管 析、宮垣朝光、大松華子、大河内仁志、佐藤伸一
  • Organizer: 第８回国際研究皮膚科学会
  • Place of Presentation: エジンバラ、スコットランド
• [Presentation] 菌状息肉症・セザリー症候群におけるアンギオポエチンの役割 (2013)
  • Author(s): 菅谷 誠、川口真喜子、管 析、宮垣朝光、大松華子、藤田英樹、佐藤伸一
  • Organizer: 第53回日本リンパ網内系学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] リンパ管機能不全が皮膚免疫に与える影響 (2013)
  • Author(s): 菅谷 誠
  • Organizer: 第112回皮膚科学会総会
  • Place of Presentation: 横浜、日本
  • Invited
• [Presentation] Delayed wound healing due to increased interleukin-10 expression in mice with lymphatic dysfunction. (2012)
  • Author(s): 記村貴之、菅谷 誠、Andrew Blauvelt、大河内仁志、佐藤伸一
  • Organizer: 研究皮膚科学会第75回年次学術大会
  • Place of Presentation: ローリー、アメリカ合衆国
• [Presentation] Delayed wound healing and impaired tumor immunity in mice with lymphatic dysfunction. (2012)
  • Author(s): 菅谷 誠、記村貴之、Andrew Blauvelt、大河内仁志、佐藤伸一
  • Organizer: 日本研究皮膚科学会第37回年次学術大会・総会
  • Place of Presentation: 那覇、日本