Investigation of subpopulation of skin resident macrophages.

• Project/Area Number: 26461677
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Tohoku University
• Principal Investigator: Watabe Akiko 東北大学, 大学病院, 助教 (30422132)
• Co-Investigator(Kenkyū-buntansha): 伊藤 由美子 東北大学, 大学病院, 臨床検査技師 (00375057) ; 相場 節也 東北大学, 医学系研究科, 教授 (80159269) ; 木村 裕 東北大学, 大学病院, 助教 (90375056) ; 藤村 卓 東北大学, 医学系研究科, 助教 (50396496)
• Research Collaborator: Kakizaki Aya 東北大学, 医学系研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腫瘍随伴性マクロファージ / ケモカイン / M2 マクロファージ / 腫瘍微小環境 / M2マクロファージ / 腫瘍随伴マクロファージ / 炎症性皮膚疾患 / 抑制型免疫環境 / 制御性T細胞 / 乳房外パジェット病 / 皮膚悪性リンパ腫 / 水疱性類天疱瘡 / M２マクロファージ

Outline of Final Research Achievements

In this study, we investigated the immunomodulatory effects of cancer-specific storma on tumor-associated macrophages, using skin samples from malignant melanoma, extramammary Paget's disease and cutaneous T cell lymphoma patients. Our study suggested that these skin cancer possesses different cancer storma (e.g. IL-4, periostin, RANKL, etc.), and those stromal factors stimulate macrophages to produce several specific chemokine, such as CCL17 and CCL22, to develop immunosuppressive tumor microenvironment in each tumor. Concerning inflammatory skin disease, we evaluated the immunomodulatory function of tissue-reside macrophages in pemphigus vulgaris and bullous pemphigoid, suggesting that the chemokine production from tissue-reside macrophages play important roles in developing autoimmune bullous disease.

Research Products

• [Journal Article] A possible interaction between periostin and CD163+ skin-resident macrophages in pemphigus vulgaris and bullous pemphigoid. (2017)
  • Author(s): Fujimura T, Kakizaki A, Furudate S, Aiba S.
  • Journal Title: Experimental Dermatology Volume: 1 Issue: 12 Pages: 1-1
  • DOI: 10.1111/exd.13157
  • Peer Reviewed
• [Journal Article] Tumor-associated M2 macrophages in mycosis fungoides aquired immunomodulatory function by interferon alpha and interferon gamma. (2016)
  • Author(s): Furudate S, Fujimura T, Kakizaki A, Hidaka T, Asano M, Aiba S.
  • Journal Title: Journal of Dermatological Science Volume: 83 Issue: 3 Pages: 182-189
  • DOI: 10.1016/j.jdermsci.2016.05.004
  • Peer Reviewed
• [Journal Article] Tumor-associated macrophages in skin: how to treat their heterogeneity and plasticity. (2016)
  • Author(s): Fujimura T, Kakizaki A, Furudate S, Kambayashi Y, Aiba S.
  • Journal Title: Journal of Dermatological Science Volume: 83 Issue: 3 Pages: 167-173
  • DOI: 10.1016/j.jdermsci.2016.05.015
  • Peer Reviewed
• [Journal Article] The possible interaction between periostin expressed by cancer stroma and tumor-associated macrophages in developing mycosis fungoides. (2016)
  • Author(s): Furudate S, Fujimura T, Kakizaki A, Kambayashi Y, Asano M, Watabe A, Aiba S.
  • Journal Title: Experimental Dermatology Volume: 25 Pages: 107-112
  • Peer Reviewed
• [Journal Article] Receptor activator of nuclear factor kappa-B ligand (RANKL)/RANK signaling promotes cancer-related inflammation through M2 macrophages. (2016)
  • Author(s): Fujimura T, Kambayashi Y, Furudate S, Kakizaki A, Hidaka T, Asano M, Aiba S.
  • Journal Title: Experimental Dermatology Volume: in press
  • Peer Reviewed
• [Journal Article] The possible interaction between receptor activator of nuclear factor kappa-B ligand (RANKL) expressed by extramammary Paget cells and its ligand on dermal macrophages. (2015)
  • Author(s): Kambayashi Y, Fujimura T, Furudate S, Asano M, Kakizaki A, Aiba S.
  • Journal Title: Journal of Investigative Dermatology Volume: 135 Issue: 10 Pages: 2547-2550
  • DOI: 10.1038/jid.2015.199
  • Peer Reviewed
• [Journal Article] Receptor activator of nuclear factor kappa-B ligand (RANKL) promotes the production of CCL17 from RANK+ M2 macrophages. (2015)
  • Author(s): Fujimura T, Kambayashi Y, Furudate S, Asano M, Kakizaki A, Aiba S.
  • Journal Title: Journal of Investigative Dermatology Volume: 135 Issue: 11 Pages: 2884-2887
  • DOI: 10.1038/jid.2015.209
  • Peer Reviewed
• [Journal Article] Retrospective Evaluation of Conservative Treatment for 140 Ingrown Toenails with a Novel Taping Procedure. (2015)
  • Author(s): Watabe A, Yamasaki K, Hashimoto A, Aiba S.
  • Journal Title: Acta Dermato Venereologica Volume: 95 Pages: 1-1
  • DOI: 10.2340/00015555-2065
  • Peer Reviewed / Open Access
• [Journal Article] A possible mechanism in the recruitment of eosinophils and Th2 cells through CD163(+) M2 macrophages in the lesional skin of eosinophilic cellulitis. (2014)
  • Author(s): Fujimura T, Kambayashi Y, Furudate S, Kakizaki A, Aiba S.
  • Journal Title: European Journal of Dermatology Volume: 24 Issue: 2 Pages: 180-185
  • DOI: 10.1684/ejd.2014.2283
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comparison of CD163+ CD206+ M2 macrophages in the lesional skin of bullous pemphigoid and pemphigus vulgaris: the possible pathogenesis of bullous pemphigoid. (2014)
  • Author(s): Furudate S, Fujimura T, Kambayashi Y, Kakizaki A, Aiba S.
  • Journal Title: Dermatology Volume: 229 Issue: 4 Pages: 369-378
  • DOI: 10.1159/000365946
  • Peer Reviewed / Acknowledgement Compliant