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移植免疫研究室

研究室紹介

移植免疫研究室では、様々な臓器移植、自己免疫疾患モデル、試験管内（in vitro）の評価系を用いた移植後拒絶反応・免疫寛容の誘導・維持、自己免疫に関与する分子・細胞の機序の解明および細胞療法（Cell Based Therapy）を中心に、制御性T細胞、iPS細胞由来制御性樹状細胞（DC）、ミエロイド由来抑制細胞（MDSC）、間葉系幹細胞等を用いる免疫制御細胞療法の確立するための基礎研究を行っています。

また、新規免疫抑制剤、新規臓器保存法の開発を積極的に進めています。さらに、悪性腫瘍モデルを用いたがん免疫、新規抗がん剤の開発およびその作用機序の解明するための基礎研究を推進しています。これら研究テーマの研究成果を将来移植・再生医療、がん医療のヒトへ応用を通じて、患者のQOLの向上、医療費の削減にも繋げていきたいと考えています。

研究内容

  1. 安全かつ効果的にドナー造血幹細胞移植後キメリズム構築することで、特異的臓器移植免疫寛容の誘導を目標として目指しています。
  2. iPS細胞から制御性樹状細胞、ミエロイド由来抑制細胞への分化誘導を行い、免疫制御細胞療法を確立することを目指しています。
  3. 植免疫寛容の誘導・維持に関与する分子・細胞の機序の解明を行い、その成果を踏まえ、新規化合物の免疫抑制剤の開発を進めています。
  4. 悪性腫瘍モデルを用いたがん免疫、新規抗がん剤の開発およびその作用機序の解明するための基礎研究を推進しています。

スタッフ

RI管理室





室員

  • 胡 鑫（研究員）

業績

2023

  1. Que WT, Ueta H, Hu X, Morita-Nakagawa M, Fujino M, Ueda D, Tokuda N, Huang WX, Guo W-Z, Zhong L, Li Xiao K*. Temporal and spatial dynamics of immune cells in mouse liver transplantation revealed by mass cytometry and immunohistochemistry. iScience 26(9):107691; 2023.
  2. Ma K, Hu X, Nambu K, Ueda D, Ichimaru N, Fujino M, Li Xiao K*. Coral calcium carried hydrogen ameliorated the severity of non-alcoholic steatohepatitis induced by a choline deficient high carbohydrate fat-free diet in elderly rats. Sci Rep. 13: 11646; 2023.
  3. Shui YF, Hu X, Hirano H, Tsukamoto H, Guo W-Z, Hasumi K, Ijima F, Fujino M, Li Xiao K*. Combined phospholipids adjuvant augments anti-tumor immune responses through activated tumor-associated dendritic cells.　Neoplasia 39: 100893; 2023.
  4. Hu X, Shui YF, Hirano H, Kusano K, Guo W-Z, Fujino M, Li Xiao K*. PD-L1 antibody enhanced β-glucan antitumor effects via blockade of the immune checkpoints in a melanoma model. Cancer Immunol Immunother. 72(3): 719-731; 2023.

2022

  1. Que WT, Ma K, Hu X, Guo WZ, Li Xiao K*. Combinations of anti-GITR antibody and CD28 superagonist induce permanent allograft acceptance by generating Type 1 regulatory T cells. Science Advances 8, eabo4413; 2022.
  2. Ma K, Que WT, Hu X, Guo WZ, Zhong L, Ueda D, Gu EL, Li Xiao K*. Combinations of anti-GITR antibody and CD28 superagonist ameliorated dextran sodium sulfate-induced mouse colitis. Clin Exp Immunol 208(3): 340-350; 2022.
  3. Watanabe T, Nishio Y, Yamamoto Y, Shimizu T, Li Xiao K, Okita H, Kuroda T. Photodynamic therapy with 5-aminolevurinic acid for pediatric neuroblastoma cell line. Journal of Pediatric Surgery 57(7): 1281-1285; 2022.
  4. Jiang ZY, Zhu HT, Wang PS, Que WT, Zhong L, Li Xiao K*. Du FT. Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity. MedComm 3:e137; 2022.
  5. Ma K, Que WT, Hu X, Guo WZ, Gu EL, Zhong L, Morello V, Cazzanti M, Michieli P, Takahara T, Li Xiao K*. A MET-agonistic antibody accelerates cirrhotic liver regeneration and improves mouse survival following partial hepatectomy. Liver Transplant 28(5):782-793; 2022.

2021

  1. Shui YF, Hu X, Hirano H, Kusano K, Tsukamoto H, Li MQ, Hasumi K, Guo WZ, Li Xiao K*. β-glucan from Aureobasidium pullulans augments the anti-tumor immune responses through activated tumor-associated dendritic cells. Int Immunopharmacol 101, Part A: 108265; 2021.
  2. Zhou XB, Li SW, He SQ, Xu SJ, Cai Y, Xu SW, Li Xiao K, Gu BB, Mao XL, Ye LP. Transplantation of acellularized dermis matrix (ADM) plus fully covered metal stent to prevent stricture after circumferential endoscopic submucosal dissection of early esophageal cancer (with video). Regenerative Therapy 18: 441e446; 2021.
  3. Du XX, Que WT, Hu X, Yu X, Guo WZ, Zhang SJ, Li Xiao K*. Oridonin prolongs the survival of mouse cardiac allografts by attenuating the NF-κB/NLRP3 pathway. Frontiers in Immunology 12: 719574; 2021.
  4. Hu X, Que WT, Hirano H, Wang ZD, Nozawa N, Ishii T, Ishizuka M, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhu P, Guo WZ, Li Xiao K*. 5-ALA/SFC enhanced the antitumor effects of PD-L1 blockade via regulated exhaustion T cell metabolism in melanoma model. Cancer Science 112(7):2652-2663; 2021.
  5. Matsuda Y, Watanabe T. Li Xiao K. Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B cells. Frontiers in Immunology 12: 682334; 2021.
  6. Wang ZD, Ma K, Fujino M, Kusano K, Yi SQ, Iwai A, Li Xiao K*. The effects of oral administration of Aureobasidium pullulans-cultured fluid containing β-glucan on concanavalin A injection in mice. Heliyon 7(6): e07277; 2021.
  7. Liu C, Wang ZD, Hu X, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhu P, Li Xiao K*. 5-aminolevulinic acid combined with sodium ferrous citrate ameliorated lupus nephritis in a mouse chronic graft-versus-host disease model. Int Immunopharmacol 96:107626; 2021.
  8. Zheng QY, Zhang SJ, Guo WZ, Li Xiao K*. The unique immunomodulatory properties of MSC-derived exosomes in organ transplantation. Frontiers in Immunology 12: 659621; 2021.
  9. Hirano S, Aoki Y, Kurokawa R, Li Xiao K, Ichimaru N, Takahara S, Takefuji Y. Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study. Medical Gas Research 11(3):104-109; 2021.
  10. Li SW, Takahara T, Que WT, Fujino M, Guo WZ, Hirano S, Ye LP, Li Xiao K*. Hydrogen-rich water protects liver injury in nonalcoholic steatohepatitis though HO-1 enhancement via IL-10 and Sirt 1 signaling. Am J Physiol Gastrointestinal and Liver Physiol 320(4): G450-463; 2021.
  11. Que WT, Li Xiao K*. Regulatory T Cells for the Induction of Transplantation Tolerance. In: SG-Zheng editor. Chapter 15: T Regulatory Cells in Human Health and Diseases. Springer Publishers Inc., pp.289-302, 2021.
  12. Zhao J, Que WT, Du XX, Fujino M, Ichimaru N, Ueta H, Tokuda N, Guo WZ, Zabrocki P, Haard HD, Nonomura N, Li Xiao K*. Monotherapy with anti-CD70 antibody causes long-term mouse cardiac allograft acceptance with induction of tolerogenic dendritic cells. Frontiers in Immunology 11: 555996; 2021.
  13. Matsuda Y, Hiramitsu T, Li Xiao K, Watanabe T. Characteristics of immunoglobulin M type antibodies of different origins from the immunologic and clinical viewpoints and their application in controlling antibody-mediated allograft rejection. Pathogens 10(1), 4; 2021.

2020

  1. Wang ZD, Ma K, Liu C, Hu X, Que WT, Ito H, Takahashi K, Nakajima M, Tanaka T, Ren K, Guo WZ, Yi SQ, Li Xiao K*. 5-Aminolevulinic acid combined with sodium ferrous ameliorated liver injury in a murine acute graft-versus-host disease model by reducing inflammation responses through PGC-1α activation. Drug Discoveries & Therapeutics 14(6):304-312; 2020.
  2. Que WT, Guo WZ, Li Xiao K*. Manipulation of regulatory dendritic cells for induction transplantation tolerance. Frontiers in Immunology 11:582658; 2020.
  3. Que WT, Hu X, Fujino M, Terayama H, Sakabe K, Fukunishi N, Zhu P, Yi SQ, Yamada Y, Zhong L, Li Xiao K*. Prolonged cold ischemia time in mouse heart transplantation using supercooling preservation. Transplantation 104(9): 1879-1889; 2020.
  4. Jiang YZ, Que WT, Zhu P, Li Xiao K*. The role of diverse liver cells in liver transplantation tolerance. Frontiers in Immunology 11:1203; 2020.
  5. Sheng C, Li Xiao K*. The role of immune modulation in pathogenesis of IgA nephropathy. Frontiers in Medicine 7:92; 2020.
  6. Wang PP, Zhao MY, Chen ZH, Wu GJ, Fujino M, Chen Zhang C, Zhou WJ, Zhao MW, Hirano S, Li Xiao K*, Zhao LL. Hydrogen gas attenuates hypoxic-ischemic brain injury via regulation of the MAPK/ HO-1/PGC-1α pathway in neonatal rats. Oxid Med Cell Longev. 2020:6978784; 2020.
  7. Wang J, Liu C, Que W, Fujino M, Tong G, Yan H, Li Xiao K*. Immunomodulatory effects of Salvianolic acid B in a spontaneous abortion mouse model. J Reprod Immunol. 137:103075. 2020.

2019

  1. Liu C, Fujino M, Zhu S, Isaka Y, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhu P, Li Xiao K*. 5-ALA/SFC enhances HO-1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis. FEBS Open Bio. 9(11): 1928-1938; 2019.
  2. Liu C, Zhu P, Fujino M, Zhu S, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhuang J, Li Xiao K*. 5-ALA/SFC attenuated binge alcohol-induced gut leakiness and inflammatory liver disease in HIV transgenic rats. Alcohol Clin Exp Res. 43(8): 1651-1661; 2019.
  3. Wang J, Liu C, Fujino M, Tong G, Zhang Q, Li Xiao K*, Yan H. Stem cells as a resource for treatment infertility-related diseases. Curr Mol Med. 19(8): 539-546; 2019.
  4. Wu G, Chen Z, Wang P, Zhao M, Fujino M, Zhang C, Zhou W, Hirano SI, Li Xiao K, Zhao L. Hydrogen inhalation protects hypoxic-ischemic brain damage by attenuating inflammation and apoptosis in neonatal rats. Exp Biol Med. 244(12): 1017-1027; 2019.
  5. Zhao J, Yang XC, Fujino M, Ichimura N, Que WT, Li Xiao K*, Takahara S. Salvianolic acid B ameliorates liver injury in a murine aGvHD model by decreasing inflammatory responses via upregulation of HO-1. Transpl Immunol. 55: 101203; 2019.
  6. Toyama S, Migita O, Fujino M, Kunieda T, Kosuga M, Fukuhara Y, Nagahara Y, Li Xiao K*. Okuyama T. New treatment method for mucopolysaccharidosis type VI by liver transplantation. Pediatr Int. 261(2): 180-189; 2019.
  7. Wang Y, Zenkoh J, Gerelchuluun A, Sun L, Cai S, Li Xiao K, Tsuboi K. Administration of Dendritic Cells and Anti-PD-1 Antibody Converts X-ray Irradiated Tumors into Effective in situ Vaccines. Int J Radiat Oncol Biol Phys. 103(4): 958-969; 2019.
  8. Uto K, Sakamoto S, Que WT, Shimata K, Hashimoto S, Sakisaka M, Narita Y, Daiki Y, Zhong L, Yoshihiro K, Kurokawa R, Li Xiao K, Inomata Y, Hibi T. Hydrogen rich solution attenuates cold ischemia-reperfusion injury in rat liver transplantation. BMC Gastroenterol. 19(1): 25; 2019.
  9. Liu C, Zhu P, Fujino M, Isaka Y, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhuang J, Li Xiao K*. 5-aminolaevulinic acid (ALA), enhances heme oxygenase (HO)-1 expression and attenuates tubulointerstitial fibrosis and renal apoptosis in chronic cyclosporine nephropathy. Biochem Biophys Res Commun. 508(2): 583-589; 2019.

2018

  1. Liu C, Yang X, Zhu P, Fujino M, Ito H, Takahashi K, Nakajima M, Tanaka T, Wang J, Zhuang J, Zou HJ, Li Xiao K*. Combination of 5-aminolaevulinic acid and iron prevents skin fibrosis in murine sclerodermatous grafts-versus-host disease. Exp Dermatol. 27(10): 1104-1111; 2018.
  2. Li S, Fujino M, Ichimaru N, Kurokawa R, Hirano S, Mou L, Takahara S, Takahara T, Li Xiao K*. Molecular hydrogen protects against ischemia-reperfusion injury in a mouse fatty liver model via regulating HO-1 and Sirt1 expression. Sci Rep. 8(1): 14019; 2018.
  3. Li S, Fujino M, Takahara T, Li Xiao K*. Protective role of heme oxygenase-1 in fatty liver ischemia-reperfusion injury. Med Mol Morphol. Aug 31. 2018.
  4. Zhao M, Yang M, Que W, Zhong L, Fujino M, Li Xiao K*. Myeloid heme oxygenase-1: a new therapeutic target in anti-inflammation. Front Biosci. 23:2001-2015; 2018.
  5. Ito H, Nishio Y, Hara T, Sugihara H, Tanaka T, Li Xiao K. Oral administration of 5-aminolevulinic acid induces heme oxygenase-1 expression in peripheral blood mononuclear cells of healthy human subjects in combination with ferrous iron. Eur J Pharmacol. 833: 25-33; 2018.
  6. Hatayama N, Hirai S, Naito M, Terayama H, Araki J, Yokota H, Matsushita M, Li Xiao K, Itoh M. Preservation of rat limbs by hyperbaric carbon monoxide and oxygen. Sci Rep. 8(1): 6627; 2018.
  7. Joyce D, Fujino M, Morita M, Araki R, Fung J, Qian S, Lu L, Li Xiao K*. Induced pluripotent stem cells-derived myeloid-derived suppressor cells regulate the CD8+ T cell response. Stem Cell Res. 29:32-41; 2018.
  8. Zhou WC, Wang Y, Fujino M, Shi LM, Jin L, Li Xiao K*, Wang JC. A standardized fold change (SFC) method for microarray differential expression analysis used to reveal genes involved in acute rejection in murine allograft models. FEBS Open Bio 8(3): 481-490; 2018.

2017

  1. 38. Li S, Takahara T, Fujino M, Fukuhara Y, Sugiyama T, Li Xiao K*, Takahara S. Astaxanthin prevents ischemia-reperfusion injury of the steatotic liver in mice. PLoS One. 12(11): e0187810; 2017.
  2. 39. Yang X, Liu C, Fujino M, Yang J, Li Xiao K*, Zou HJ. A modified graft-versus-host-induced model for systemic sclerosis, with pulmonary fibrosis in Rag2-deficient mice. FEBS Open Bio 7(9): 1316-1327; 2017.
  3. 40. Cai SJ, Hou JG, Fujino M, Zhang Q, Ichimaru N, Takahara S, Araki R, Lu L, Chen JM, Zhuang J, Zhu P, Li Xiao K*. iPSC-derived Regulatory Dendritic Cells Inhibit Allograft Rejection via Generating Alloantigen-specific Regulatory T Cells. Stem Cell Reports 8(5): 1174-1189; 2017.
  4. 41. Yang XC, Fujino M, Cai SJ, Li SW, Liu, C, Li Xiao K*. Genetic polymorphisms of cytotoxic T-lymphocyte antigen 4 in primary biliary cholangitis: a meta-analysis. Journal of Immunology Research 2017:5295164; 2017.
  5. 42. Abe T, Yazawa K, Fujino M, Imamura R, Hatayama N, Kakuta Y, Tsutahara K, Okumi M, Ichimaru, Kaimori J, Isaka Y, Seki K, Takahara S, Li Xiao K*, Nonomura. N High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation. Lab Invest 97(4): 468-477; 2017.

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