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The expression of Foxp3 protein by retroviral vector-mediated gene transfer of Foxp3 in C57BL/6 mice

C57BL/6 마우스에서 Retroviral 벡터를 이용한 Foxp3 유전자의 도입에 의한 Foxp3 단백의 발현 양상

  • Hwang, Insun (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University) ;
  • Ha, Danbee (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University) ;
  • Bing, So Jin (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University) ;
  • Jeon, Kyong-Leek (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University) ;
  • Ahn, Ginnae (Department of Marine Life Sciences, Jeju National University) ;
  • Kim, Dae Seung (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University) ;
  • Cho, Jinhee (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University) ;
  • Lim, Jaehak (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University) ;
  • Im, Sin-Hyeog (School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology (GIST)) ;
  • Hwang, Kyu-Kye (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University) ;
  • Jee, Youngheun (College of Veterinary Medicine and Applied Radiological Institute, Jeju National University)
  • 황인선 (제주대학교 수의과대학 수의학과) ;
  • 하단비 (제주대학교 수의과대학 수의학과) ;
  • 빙소진 (제주대학교 수의과대학 수의학과) ;
  • 전경익 (제주대학교 수의과대학 수의학과) ;
  • 안긴내 (제주대학교 해양과학대학 해양생명과학과) ;
  • 김대승 (제주대학교 수의과대학 수의학과) ;
  • 조진희 (제주대학교 수의과대학 수의학과) ;
  • 임재학 (제주대학교 수의과대학 수의학과) ;
  • 임신혁 (광주과학기술원 생명과학부 면역조절연구실) ;
  • 황규계 (제주대학교 수의과대학 수의학과) ;
  • 지영흔 (제주대학교 수의과대학 수의학과)
  • Received : 2011.12.09
  • Accepted : 2012.09.19
  • Published : 2012.09.30

Abstract

The maintenance of peripheral immune tolerance and prevention of chronic inflammation and autoimmune disease require $CD4^{+}CD25^{+}$ T cells (regulatory T cells). The transcription factor Foxp3 is essential for the development of functional, regulatory T cells, which plays a prominent role in self-tolerance. Retroviral vectors can confer high level of gene transfer and transgene expression in a variety of cell types. Here we observed that following retroviral vector-mediated gene transfer of Foxp3, transductional Foxp3 expression was increased in the liver, lung, brain, heart, muscle, spinal cord, kidney and spleen. One day after vector administration, high levels of transgene and gene expression were observed in liver and lung. At 2 days after injection, transductional Foxp3 expression level was increased in brain, heart, muscle and spinal cord, but kidney and spleen exhibited a consistent low level. This finding was inconsistent with the increase in both $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell frequencies observed in peripheral immune cells by fluorescence-activated cell-sorting (FACS) analysis. Retroviral vector-mediated gene transfer of Foxp3 did not lead to increased numbers of $CD4^{+}CD25^{+}$ T cell and $CD4^{+}Foxp3^{+}$ T cell. These results demonstrate the level and duration of transductional Foxp3 gene expression in various tissues. A better understanding of Foxp3 regulation can be useful in dissecting the cause of regulatory T cells dysfunction in several autoimmune diseases and raise the possibility of enhancing suppressive functions of regulatory T cells for therapeutic purposes.

Acknowledgement

Supported by : 학술진흥재단, 한국해양과학기술진흥원