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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation
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Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation

机译：细胞可渗透的Foxp3蛋白可减轻与炎症性肠病和过敏性气道炎症相关的自身免疫性疾病

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摘要

Foxp3 is a key transcription factor for differentiation and function of regulatory T (Treg) cells that is critical for maintaining immunolog-ical self-tolerance. Therefore, increasing Treg function by Foxp3 transduction to regulate an inflammatory immune response is an important goal for the treatment of autoimmune and allergic diseases. Here we have generated a cell-permeable Foxp3 protein by fusion with the unique human HHph-1 -PTD (protein transduction domain), examined its regulatory function in T cells, and characterized its therapeutic effect in autoimmune and allergic disease models. HHph-1-Foxp3 was rapidly and effectively transduced into cells within 30 min and conferred suppressor function to CD4~+CD25~-T cells as well as directly inhibiting T-cell activation and proliferation. Systemic delivery of HHph-1 Foxp3'remarkably inhibited the autoimmune symptoms of scurfy mice and the development of colitis induced by scurfy or wild-type CD4 T cells. Moreover, intranasal delivery of HHph-1-Foxp3 strongly suppressed ovalbumin-induced allergic airway inflammation. These results demonstrate the clinical potential'of the cell-permeable recombinant HHph-1-Foxp3 protein in autoimmune and hypersensitive allergic diseases.
机译：Foxp3是调节性T细胞（Treg）分化和功能的关键转录因子，对于维持免疫学自我耐受性至关重要。因此，通过Foxp3转导增加Treg功能以调节炎性免疫应答是治疗自身免疫和过敏性疾病的重要目标。在这里，我们通过与独特的人类HHph-1-PTD（蛋白质转导域）融合产生了可渗透细胞的Foxp3蛋白，检查了其在T细胞中的调节功能，并表征了其在自身免疫和过敏性疾病模型中的治疗作用。 HHph-1-Foxp3在30分钟内迅速有效地转导到细胞中，并赋予CD4〜+ CD25〜-T细胞抑制功能，并直接抑制T细胞的活化和增殖。 HHph-1 Foxp3'的全身递送显着抑制了坏血病小鼠的自身免疫症状以及坏血病或野生型CD4 T细胞诱导的结肠炎的发展。此外，HHph-1-Foxp3的鼻内给药强烈抑制卵清蛋白诱导的过敏性气道炎症。这些结果证明了细胞可渗透的重组HHph-1-Foxp3蛋白在自身免疫性和超敏性过敏性疾病中的临床潜力。

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  • 作者

    Je-Min Choi; Jae-Hun Shin; Myung-Hyun Sohn; Martha J. Harding; Jong-Hyun Park; Zuzana Tobiasova; Da-Young Kim; Stephen E. Maher; Wook-Jin Chae; Sung-Ho Park; Chun-Geun Lee; Sang-Kyou Lee; Alfred L. M. Bothwell;

  • 作者单位

    Department of Life Science, Hanyang University, Seoul 133-791, Republic of Korea Hanyang Biomedical Research Institute, Seoul 133-791, Republic of Korea Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;

    rnDepartment of Biotechnology, National Creative Research Initiatives Center for Inflammatory Response Modulation, Yonsei University, Seoul 120-749, Republic of Korea Specific Organs Cancer Branch, Research Institute National Cancer Center, Goyang, Gyeonnggi 410-769, Republic of Korea;

    rnDepartment of Pediatrics and Institute of Allergy, Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 102-752, Republic of Korea;

    rnSection of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06519;

    rnDepartment of Biotechnology, National Creative Research Initiatives Center for Inflammatory Response Modulation, Yonsei University, Seoul 120-749, Republic of Korea;

    rnDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;

    rnDepartment of Biotechnology, National Creative Research Initiatives Center for Inflammatory Response Modulation, Yonsei University, Seoul 120-749, Republic of Korea;

    rnDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;

    rnDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;

    rnDepartment of Biotechnology, National Creative Research Initiatives Center for Inflammatory Response Modulation, Yonsei University, Seoul 120-749, Republic of Korea;

    rnSection 6f Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520;

    rnDepartment of Biotechnology, National Creative Research Initiatives Center for Inflammatory Response Modulation, Yonsei University, Seoul 120-749, Republic of Korea;

    rnDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    protein transduction domain; immunotherapy; autoimmunity; allergy;

    机译：蛋白质转导结构域;免疫疗法自身免疫过敏;

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