ガレクチン9による免疫制御性マクロファージの誘導とその機構

2012 年度 研究成果報告書

• 研究課題/領域番号: 22590360
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 実験病理学
• 研究機関: 香川大学
• 研究代表者: 平島 光臣 香川大学, 医学部, 客員研究員 (70109700)
• 研究分担者: 大水 総一 香川大学, 医学部, 助教 (00444729) ; 仁木 敏朗 香川大学, 医学部, 助教 (40558508)
• 研究期間 (年度): 2010 – 2012
• キーワード: ガレクチン 9 / 免疫学 / 癌 / 炎症 / マクロファージ

研究概要

表記課題による成果に合わせて、国内外の多くの共同研究によってGalectin-9 が免疫系細胞以外の細胞機能の制御に重要な作用を示すことを明らかにされた。Galectin がカビやカイメン等の下等動物から人まで長く保存されていることから免疫のみならず感染等を含む多くのストレスに対する防御因子として存在してきたと考えられる。

研究成果

• [雑誌論文] HCV-infected hepatocytes drive CD4+ CD25+ Foxp3+ regulatory T-cell development through the Tim-3/Gal-9 pathway. (2013)
  • 著者名/発表者名: Ji XJ, Ma CJ, Wang JM, Wu XY, Niki T,Hirashima M, Moorman JP, Yao ZQ
  • 雑誌名: Eur J Immunol. 巻: 43 ページ: 458-67
• [雑誌論文] A possible role of galectin-9 in the pulmonary fibrosis of patients with interstitial pneumonia (2013)
  • 著者名/発表者名: Matsumoto N, Katoh S, Yanagi S, Arimura Y, Tokojima M, Ueno M, Hirashima M, Nakazato M.
  • 雑誌名: Lung 巻: 191 ページ: 191-8
• [雑誌論文] Self-association of the galectin-9 C-terminal domain via the opposite surface of the sugar-binding site (2013)
  • 著者名/発表者名: Nonaka Y, Ogawa T, Oomizu S, Nakakita SI, Nishi N, Kamitori S,Hirashima M, Nakamura T.
  • 雑誌名: J Biochem. 巻: 153 ページ: 463-71
• [雑誌論文] Galectin-9 functionally impairs natural killer cells in humans and mice. (2013)
  • 著者名/発表者名: Golden-Mason L, McMahan RH, Strong M, Reisdorph R, Mahaffey S, Palmer BE, Cheng L, Kulesza C, Hirashima M, Niki T, Rosen HR.
  • 雑誌名: J Virol 巻: 87 ページ: 4838-45
• [雑誌論文] Galectin-9 in cancer therapy (2013)
  • 著者名/発表者名: Fujihara S, Mori H, Kobara H, Rafiq K, Niki T, Hirashima M, Masaki T.
  • 雑誌名: Recent Pat Endocr Metab Immune Drug Discov 巻: 7 ページ: 130-7
• [雑誌論文] Galectin-9 Ameliorates Clinical Severity of MRL/lpr Lupus-Prone Mice by Inducing Plasma Cell Apoptosis Independently of Tim-3. (2013)
  • 著者名/発表者名: Moritoki M, Kadowaki T, Niki T, Nakano D, Soma G, Mori H, Kobara H, Masaki T, Kohno M, Hirashima M.
  • 雑誌名: PLoS One 巻: 8 ページ: e60807
• [雑誌論文] The increase of plasma galectin-9 in a patient with insulin allergy: a case report. (2012)
  • 著者名/発表者名: H. Chagan-Yasutan, B. Shiratori, UR. Siddiqi, H. Saitoh, Y. Ashino, T.Arikawa, M. Hirashima, T. Hattori.
  • 雑誌名: Clin Mol Allergy 巻: 8 ページ: 12(1-4)
• [雑誌論文] Galectin-9 signaling prolongs survival in murine lung-cancer by inducing macrophages to differentiate into plasmacytoid dendritic cell-like macrophages. (2012)
  • 著者名/発表者名: Kadowaki T, Arikawa T, Shinonaga R, Oomizu S, Inagawa H, Soma G, Niki T, Hirashima M
  • 雑誌名: Clin Immunol 巻: 142 ページ: 296-307
• [雑誌論文] Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner (2012)
  • 著者名/発表者名: Oomizu S, Arikawa, T, Kadowaki T, Ueno M, Nishi N, Yamauchi A, Hirashima M
  • 雑誌名: Clin Immunol 巻: 143 ページ: 51-58
• [雑誌論文] Galectin-9 ameliorates herpes simplex-induced inflammation through apoptosis (2012)
  • 著者名/発表者名: Shim JA, Park S, Lee ES, Niki T, Hirashima M, Sohn S
  • 雑誌名: Immunobiology 巻: 217 ページ: 657-66
• [雑誌論文] Tim-3 is an inducible human NK cell receptor that enhances interferon gamma production in response to galectin-9 (2012)
  • 著者名/発表者名: MK. Gleason, TR. Lenvik, V. McCullar, M.Felices, MS. O'Brien, SA. Cooley, MR. Verneris, F. Cichocki, CJ. Holman, A.Panoskaltsis-Mortari, T. Niki, M.Hirashima, B.R. Blazar, JS. Miller
  • 雑誌名: Blood 巻: 119 ページ: 3064-72
• [雑誌論文] IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma (2012)
  • 著者名/発表者名: ZZ. Yang, DM. Grote, SC. Ziesmer, T. Niki, M. Hirashima, AJ. Novak, TE. Wizig, SM. Ansell.
  • 雑誌名: J. Clin Invest 巻: 122 ページ: 1271-82
• [雑誌論文] Galectin-9 binding to Tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection (2012)
  • 著者名/発表者名: S. Elahi, T. Niki, M. Hirashima, H. Horton.
  • 雑誌名: Blood 巻: 120 ページ: 682-90
• [雑誌論文] The glycan-binding protein Galectin-9 has direct apoptotic activity towards melanoma cells (2012)
  • 著者名/発表者名: Wiersma VR, de Bruyn M, van Ginkel RJ, Sigar E, HirashimaM, Niki T, Nishi N, Samplonius DF, Helfrich W, Bremer E.
  • 雑誌名: J Invest Dermatol 巻: 132 ページ: 2302-5
• [雑誌論文] Contrasting acute graft-versus-host disease effects ofTim-3/galectin-9 pathway blockade dependent upon the presence ofdonor regulatory T cells. (2012)
  • 著者名/発表者名: Veenstra RG, Taylor PA, Zhou Q, Panoskaltsis-Mortari A, Hirashima M, Flynn R, Liu D, Anderson AC, Strom TB, Kuchroo VKK, Blazar BR.
  • 雑誌名: Blood 巻: 120 ページ: 682-90
• [雑誌論文] A novel monoclonal antibody fordetection ofgalectin-9 intissue sections: application tohuman tissues infected byoncogenic viruses. (2012)
  • 著者名/発表者名: Barjon C, Niki T, Verillaud B, Opolon P, Bedossa P,Hirashima M, Blanchin S, Wassef M, Rosen HR, Jimenez AS, Wei M, Busson P
  • 雑誌名: Infect Agent Cancer 巻: 7 ページ: 16
• [雑誌論文] TNFRSF25 Agonistic Antibody andGalectin-9 Combination Therapy Controls Herpes Simplex Virus-Induced Immunoinflammatory Lesions. (2012)
  • 著者名/発表者名: J Reddy PB, Schreiber TH, Rajasagi NK, Suryawanshi A, Mulik S, Veiga-Parga T, Niki T, Hirashima M, Podack ER, Rouse BT
  • 雑誌名: J Virol 巻: 86 ページ: 10606-20
• [雑誌論文] Tumor-infiltrating DCssuppress nucleic acid-mediated innate immune responses through interactions between thereceptor TIM-3 and thealarmin HMGB1. (2012)
  • 著者名/発表者名: Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colgan JD, Hirashima M, Uede T, Takaoka A, Yagita H, Jinushi M.
  • 雑誌名: Nat Immunol 巻: 13 ページ: 832-42
• [雑誌論文] Rapid Decrease ofPlasma Galectin-9 Levels inPatients with Acute HIVInfection after Therapy (2012)
  • 著者名/発表者名: Saitoh H, Ashino Y, Chagan-Yasutan H, Niki T, Hirashima M, Hattori T.
  • 雑誌名: Tohoku J Exp Med 巻: 228 ページ: 157-61
• [雑誌論文] Cell surface galectin-9 expressing th cells regulate Th17 and Foxp3+ Treg development by galectin-9 secretion (2012)
  • 著者名/発表者名: Oomizu S, Arikawa T, Niki T, Kadowaki T, Ueno M, Nishi N, Yamauchi A, Hattori T, Masaki T, Hirashima M.
  • 雑誌名: PLoS One 巻: 7 ページ: e48574
• [雑誌論文] Galectin-9 ameliorates acute GVH disease through the induction of T-cell apoptosis (2011)
  • 著者名/発表者名: Sakai K., Kawata E., Ashihara E., Nakagawa Y., Yamauchi A., Yao H., Nagao R., Tanaka R., Yokota A., Takeuchi M., Hirai H., Kimura S., Hirashima M., Yoshimura N., Maekawa T.
  • 雑誌名: Eur J Immunol 巻: 41 ページ: 67-75
• [雑誌論文] Dysregulation of TIM-3-galectin-9 pathway in the cystic fibrosis airways. (2011)
  • 著者名/発表者名: Vega-Carrascal I, Reeves EP, Niki T, Arikawa T, McNally P, O'Neill SJ, Hirashima M, McElvaney NG.
  • 雑誌名: J. Immunol. 巻: 186 ページ: 2897-909
• [雑誌論文] Endogenous galectin-1 and acute inflammation: emerging notion of a galectin-9 pro-resolving effect. (2011)
  • 著者名/発表者名: Iqbal AJ, Sampaio AL, Maione F, Greco KV, Niki T, Hirashima M, Perretti M, Cooper D.
  • 雑誌名: Am. J. Pathol. 巻: 178 ページ: 1201-09
• [雑誌論文] Galectin-9 administration ameliorates CVB3 induced myocarditis by promoting the proliferation of regulatory T cells and alternatively activated Th2 cells. (2011)
  • 著者名/発表者名: Lv K, Xu W, Wang C, Niki T, Hirashima M, Xiong S.
  • 雑誌名: Clin Immunol 巻: 140 ページ: 92-101
• [雑誌論文] Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. (2011)
  • 著者名/発表者名: Zhou Q, Munger ME, Veenstra RG, Weigel BJ, Hirashima M, Munn DH, Murphy WJ, Azuma M, Anderson AC, Kuchroo VK, Blazar BR.
  • 雑誌名: Blood 巻: 117 ページ: 4501-10
• [雑誌論文] Galectin-9 attenuates acute lung injury by expanding CD14- plasmacytoid dendritic cell-like macrophages. (2011)
  • 著者名/発表者名: Kojima K, Arikawa T, Saita N, Goto E, Tsumura S, Tanaka R, Masunaga A, Niki T, Oomizu S, Hirashima M, Kohrogi H.
  • 雑誌名: Am J Respir Crit Care Med 巻: 184 ページ: 328-39
• [雑誌論文] Influence of galectin-9/Tim-3 interaction on herpes simplex virus-1 latency. (2011)
  • 著者名/発表者名: Reddy PB, Sehrawat S, Suryawanshi A, Rajasagi NK, Mulik S, Hirashima M, Rouse BT
  • 雑誌名: J Immunol 巻: 187 ページ: 5748-55
• [雑誌論文] Galectin-9 expands immunosuppressive macrophages to ameliorate T cell-mediated lung inflammation. (2010)
  • 著者名/発表者名: Arikawa T, Saita N, Oomizu S, Ueno M, Matsukawa A, Katoh S, Kojima K, Nagahara K, Miyake M, Yamauchi A, Kohrogi H, and Hirashima M.
  • 雑誌名: Eur J Immunol 巻: 40 ページ: 548-58
• [雑誌論文] Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways (2010)
  • 著者名/発表者名: T. Kobayashi, J. Kuroda, E.Ashihara, S. Oomizu, Y. Terui, A. Taniyama, S. Adachi, T. Takagi, M. Yamamoto, N Sasaki, S Horiike, K. Hatake, A. Yamauchi, M.Hirashima, M. Taniwaki.
  • 雑誌名: Leukemia 巻: 24 ページ: 843-50
• [雑誌論文] Galectin-9 induces osteoblast differentiaion through the CD44/Smad signaling pathway. (2010)
  • 著者名/発表者名: R. Tanikawa, T.Tanikawa, M. Hirashima, A. Yamauchi, Y.Tanaka.
  • 雑誌名: BBRC 巻: 394 ページ: 317-22
• [雑誌論文] Targeting activating transcription factor 3 by galectin-9 induces apoptosis and overcomes various types of treatment resistance in chronic myelogenous leukemia. (2010)
  • 著者名/発表者名: J. Kuroda, M.Yamamoto, H. Nagoshi, T. Kobayashi, N. Sasaki, Y Shimura, S Horiike, S. Kimura, A. Yamauchi, M. Hirashima, M.Taniwaki.
  • 雑誌名: Molecular Cancer Research 巻: 8 ページ: 994-1001
• [雑誌論文] Tim-3/galectin-9 pathway: regulation of Th1 immunity through promotion of CD11b+Ly-6G+ myeloid cells., Valerie Dardalhon, AC. Anderson (2010)
  • 著者名/発表者名: J.Karman, L. Apetoh, R. Chandwaskar, DH. Lee, M.Cornejo, N. Nishi, A. Yamauchi, FJ. Quintana, RA. Sobel, M. Hirashima, VK. Kuchroo.
  • 雑誌名: J. Immunol. 巻: 185 ページ: 1383-92
• [雑誌論文] Galectin-9 trafficking regulates apical-basal polarity in Madin-Darby canine kidney epithelial cells. (2010)
  • 著者名/発表者名: Rashmi Mishra, Michal Grzybek, Toshiro Niki, Mitsuomi Hirashima, Kai Simons.
  • 雑誌名: PNAS 巻: 107 (41) ページ: 17633-38
• [雑誌論文] A crucial role for Kupffer cell-derived galectin-9 in regulation of T cell immunity in chronic hepatitis C infection. (2010)
  • 著者名/発表者名: John A. Mengshol, Lucy Golden-Mason, Tomohiro Arikawa, Maxwell Smith, Toshiro Niki, Ryan McWilliams, Jessica Randall, Rachel McMahan, Manu Rangachari, Evgenia Dobrinskikh, Pierre Busson, Stephen J. Polyak, Mitsuomi Hirashima, Hugo R. Rosen.
  • 雑誌名: Plos One 巻: 5(3) ページ: e9504
• [雑誌論文] Galectin-9/TIM-3 interaction regulates virus-specific primary and memory CD8+ T cell response (2010)
  • 著者名/発表者名: Sharvan Sehrawat, Pradeep B J Reddy, Naveen Rajasagi, Amol Suryawanshi, Mitsuomi Hirashima, Barry T Rouse.
  • 雑誌名: PLOS Pathogens 巻: 6 (5) ページ: e1000882
• [雑誌論文] Determination of carbohydratebinding preferences of human galectins with carbohydrate microarrays. (2010)
  • 著者名/発表者名: T.Horlacher, M A. Oberli, DB. Werz, LH. Krock, S. Bufali, B. Stocker, R. Mishra, J. Sobek, K. Simons, M. Hirashima, T. Niki, PH. Seeberger.
  • 雑誌名: ChemBioChem 巻: 11 ページ: 1563-73
• [雑誌論文] X-ray structures of human galectin-9 C-terminal domain in complexes with a biantennary oligosaccharide and sialyllactose (2010)
  • 著者名/発表者名: H. Yoshida, M. Teraoka, N. Nishi, S. Nakakita, T. Nakamura, M.Hirashima. S. Kamitori.
  • 雑誌名: J Biol Chem 巻: 285 ページ: 36969-76