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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Conversion of Th2 memory cells into Foxp3~+ regulatory T cells suppressing Th2-mediated allergic asthma
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Conversion of Th2 memory cells into Foxp3~+ regulatory T cells suppressing Th2-mediated allergic asthma

机译：Th2记忆细胞转化为抑制Th2介导的过敏性哮喘的Foxp3〜+调节性T细胞

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摘要

Genetic and epigenetic programming of T helper (Th) cell subsets during their polarization from naive Th cells establishes long-lived memory Th cells that stably maintain their lineage signatures. However, whether memory Th cells can be redifferentiated into another Th lineage is unclear. In this study, we show that Ag-specific memory Th cells were redifferentiated into Foxp3~+ T cells by TGF-β when stimulated in the presence of all-trans retinoic acid and rapamycin. The "converted" Foxp3~+ T cells that were derived from Th2 memory cells down-regulated GATA-3 and IRF4 and produced little IL-4, IL-5, and IL-13. Instead, the converted Foxp3~+ T cells suppressed the proliferation and cytokine production of Th2 memory cells. More importantly, the converted Foxp3~+ T cells efficiently accumulated in the airways and significantly suppressed Th2 memory cell-mediated airway hyperreactivity, eosinophilia, and allergen-specific IgE production. Our findings reveal the plasticity of Th2 memory cells and provide a strategy for adoptive immunotherapy for the treatment of allergic diseases.
机译：T辅助（Th）细胞子集从幼稚Th细胞极化过程中的遗传和表观遗传程序建立了长寿的记忆Th细胞，这些细胞稳定地维持了其谱系特征。但是，尚不清楚记忆Th细胞是否可以重新分化为另一个Th谱系。在这项研究中，我们表明在全反式维甲酸和雷帕霉素的存在下，TGF-β可以将Ag特异性记忆Th细胞再分化为Foxp3〜+ T细胞。来源于Th2记忆细胞的“转化的” Foxp3 + T细胞下调了GATA-3和IRF4，产生了很少的IL-4，IL-5和IL-13。相反，转化的Foxp3 + T细胞抑制了Th2记忆细胞的增殖和细胞因子的产生。更重要的是，转化的Foxp3〜+ T细胞有效地积聚在气道中，并显着抑制了Th2记忆细胞介导的气道反应过度，嗜酸性粒细胞增多和过敏原特异性IgE的产生。我们的发现揭示了Th2记忆细胞的可塑性，并为过继性免疫疗法治疗过敏性疾病提供了策略。

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  • 作者

    Byung-Seok Kim; Il-Kyu Kim; Young-Jun Park; Yun-Sun Kim; Yeon-Jeong Kim; Woo-Sung Chang; Yoon-Sook Lee; Mi-Na Kweon; Yeonseok Chung; Chang-Yuil Kang;

  • 作者单位

    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;

    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;

    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;

    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;

    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;

    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;

    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea;

    Mucosal Immunology Section, International Vaccine Institute, Seoul 151-919, Korea;

    Department of Immunology, M. D. Anderson Cancer Center, Houston, TX 77030;

    Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology and College of Pharmacy,Seoul National University, Seoul 151-742, Korea;

  • 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

    all-trans retinoic acid; immune tolerance; immunotherapy; plasticity rapamycin;

    机译：全反式维甲酸免疫耐受免疫疗法可塑性雷帕霉素;

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