国立研究開発法人 国立成育医療研究センター National Center for Child Health and Development

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Scholar & Enterprise

Scholar & Enterprise

Division of Radiation Safety

Our division investigates the fundamental events of immune cells during immune response to transplantation antigens and ischemia/reperfusion injury. We aim to understand the basic processes that control T-cell activation and tolerance, and develop novel immunosuppressive agents, antibodies, and siRNA using rodent heart and liver transplantation models. We have also proposed several new approaches for cell-based immunotherapy, including iPS-cell-derived regulatory dendritic cells, myeloid-derived suppressor cells, mesenchymal stem cells, and gene therapy in transplant rejection. Furthermore, we have developed a novel non-invasive positron emission tomography (PET) imaging method for the evaluation of acute allograft rejection and immunosuppressive therapy efficacy. We are currently building a biomarker search system for liver transplantation patients.

Through our research, we aim to:

  1. Gain mechanistic insights into immune tolerance induction and maintenance;
  2. Establish new approaches for cell-based immunotherapy;
  3. Develop novel biomarkers and methods for transplant rejection diagnosis;
  4. Create novel immunosuppressive agents, antibodies, siRNA, etc.;
  5. Devise new solutions and methods for organ preservation.




  • Hu Xin



1.    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 In press; 2020.

2.    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.

3.    Sheng C, Li Xiao K*. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy. Frontiers in Medicine 7:92; 2020.

4.    Dai Y, Yi K, Shimada K, Ren K, Wang Z, Terayama H, Li Xiao K, Yi SQ. Anatomy of the coronary arteries in fetal pigs: comparison with human anatomy. Anat Sci Int. 95(2): 265-276; 2020.

5.    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.

6.    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.


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.     Liu NB, Wu M, Chen C, Fujino M, Huang JS, Zhu P, Li Xiao K*. Novel Molecular Targets Participating in Myocardial Ischemia-Reperfusion Injury and Cardioprotection. Cardiol Res Pract. 2019:6935147; 2019.

4.     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.

5.     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.

6.     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.

7.     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.

8.     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.

9.     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.

10.  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.


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. 2018 Aug 31. 

4.     Zhao M, Yang M, Que W, Zhong L, Fujino MLi 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, Hayato Terayama, 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.     Cheng XY, Li SY, Mao CJ, Wang MX, Chen J, Wang F, Wang GH, Deng WB, Li Xiao K, Liu CF. Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy. Neuroscience 371:288-295; 2018.

9.     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.


1.     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.     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.     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.     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.     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.


1.    Zhao M, Zhu P, Fujino M, Nishio Y, Chen J, Ito H, Takahashi K, Nakajima M, Tanaka T, Zhao L, Zhuang J, Li Xiao K*. 5-Aminolevulinic acid with sodium ferrous citrate induces autophagy and protects cardiomyocytes from hypoxia-induced cellular injury through MAPK-Nrf-2-HO-1 signaling cascade. Biochem Biophys Res Commun. 28; 479(4): 663-669; 2016.

2.    Zhao M, Zhu P, Fujino M, Zhuang J, Guo H, Sheikh I, Zhao L, Li Xiao K*. Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies. Int J Mol Sci. 10:17(12). pii: E2078, 2016

3.    Ichiishi E, Li Xiao K, Iorio EL. Oxidative Stress and Diseases: Clinical Trials and Approaches. Oxid Med Cell Longev. 2016:3458276; 2016.

4.    Hatayama N, Inubushi M, Naito M, Hirai S, Jin YN, Tsuji AB, Seki K, Itoh M, Saga T, Li Xiao K*. Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen. Sci Rep. 6:32120; 2016.

5.    Fujino M, Zhu P, Cai S, Nishio Y, Zhuang J, Li Xiao K*. MicroRNAs involved in acute rejection and tolerance in murine cardiac allografts. Exp Clin Transplant 14(4): 424-30; 2016.

6.    Ji H, Li Xiao K. Oxidative stress in atopic dermatitis. Oxid Med Cell Longev. 2016:2721469; 2016.

7.    Nishio Y, Fujino M, Cai S, Kitajima Y, Saito T, Tsumura H, Ito M, Ito Y, Nagahara Y, Li Xiao K*. Impaired CD98 signaling protects against graft-versus-host disease by increasing regulatory T cells. Transpl Immunol 35:34-9, 2016.

8.    Cai S, Ichimaru N, Zhao M, Fujino M, Ito H, Takahashi K, Ota U, Nakajima M, Tanaka T, Nonomura N, Li Xiao K*, Takahara S. Prolonged mouse cardiac graft cold storage via attenuating ischemia-reperfusion injury using a new antioxidant-based preservation solution. Transplantation 100(5): 1032-40, 2016.

9.    Li S, Takahara T, Li Xiao K*, Fujino M, Sugiyama T, Tsukada K, Liu C, Kakuta Y, Nonomura N, Ito H, Takahashi K, Nakajima M, Tanaka T, Takahara S. 5-aminolevulinic acid combined with ferrous iron ameliorate ischemia-reperfusion injury in the mouse fatty liver model. Biochem Biophys Res Commun. 19; 470(4): 900-6, 2016.


1.    Hirano H, Hasumi K, Li Xiao K*. Stem cell-derived immunosuppressive cells therapy in organ transplantation. In: Chen GF, Qian SG editors. Chapter 21: Current Immunosuppressive Therapy in Organ Transplantation. New York: Nova Science Publishers Inc., pp.557-574, 2015.

2.    Fujino M, Nishio Y, Ito H, Tanaka T, Li Xiao K*. 5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction. Int Immunopharmacol. S1567-5769 (15) 30202-2, 2015.

3.    Hou JG, Fujino M, Cai SJ, Ding Q, Li Xiao K*. Noninvasive monitoring and evaluation of the renal structure and function in a mouse model of unilateral ureteral occlusion using microcomputed tomography. Int Surg 100(7-8): 1237-43; 2015.

4.    Zhao M, Guo H, Chen J, Fujino M, Ito H, Takahashi K, Abe F, Nakajima M, Tanaka T, Wang J, Huang H, Zheng S, Hei M, Li J, Huang S, Li J, Ma X, Chen Y, Zhao L, Zhuang J, Zhu P, Li Xiao K*. 5-Aminolevulinic acid combined with sodium ferrous citrate ameliorates H2O2-induced cardiomyocyte hypertrophy via activation of the MAPK/Nrf2/HO-1 pathway. Am J Physiol Cell Physiol 308:C665-672; 2015.

5.    Zhao MY, Chen JJ, Zhu P, Fujino M, Takahara T, Toyama S, Tomita A, Zhao LL, Yang ZC, Hei MY, Zhong L, Zhuang J, Kimura S, Li Xiao K*. Dihydroquercetin (DHQ) ameliorated concanavalin A-induced mouse experimental fulminant hepatitis and enhanced HO-1 expression through MAPK/Nrf2 antioxidant pathway in RAW cells. Int Immunopharmacol S1567-5769 (15) 00196-4; 2015.

6.    Zhang Q, Fujino M, Xu JH, and Li Xiao K*.The role and potential therapeutic application of myeloid-derived suppressor cells in allo- and auto-immunity. Mediators Inflamm 2015: 421927; 2015.

7.    Hou JG, Fujino M, Cai SJ, Ding Q, Li Xiao K*. Noninvasive monitoring of mouse renal allograft rejection using micro-CT. Ann Surg Treat Res 88(5): 276-280; 2015.

8.    Zhang Q, Ichimaru N, Higuchi S, Cai SJ, Hou JG, Fujino M, Nonomura N, Kobayashi M, Ando H, Uno A, Sakurai K, Mochizuki S, Adachi Y, Ohno N, Zou HJ, Xu JH, Li Xiao K*.  Takahara S.  Permanent acceptance of mouse cardiac allografts with CD40 siRNA to induce regulatory myeloid cells by use of a novel polysaccharide siRNA delivery system. Gene Ther 22(3):1-10; 2015.

9.    Hou JG, Zhang Q, Fujino M, Cai SJ, Ito H, Takahashi K, Abe F, Nakajima M, Tanaka T, Xu JH, Zou HJ, Ding Q, Li Xiao K*. 5-aminolaevulinic acid with ferrous iron induces permanent cardiac allograft acceptance in mice via the induction of regulatory cells. J Heart Lung Transplant 34(2): 254-63; 2015.

10. Shigeta T, Sakamoto S, Li Xiao K, Cai SJ, Liu C, Kurokawa R, Nakazawa A, Kasahara M, Uemoto S. Luminal injection of hydrogen-rich solution attenuates intestine ischemia-reperfusion injury in rats. Transplantation 99(3): 500-7; 2015.