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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3~+ regulatory T cells
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GARP (LRRC32) is essential for the surface expression of latent TGF-β on platelets and activated FOXP3~+ regulatory T cells

机译：GARP（LRRC32）对于潜在TGF-β在血小板和活化的FOXP3〜+调节性T细胞上的表面表达至关重要

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摘要

TGF-β family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-β is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFβ-binding protein (LTBP) to produce a large latent form. Latent TGF-β is also found on the surface of activated FOXP3~+ regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucire rich repeat molecule of unknown function, is critical for tethering TGF-β to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-β and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-β expression on activated Tregs and recombinant latent TGF-β1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-β on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism.
机译：TGF-β家族成员是具有多种调节功能的高度多效性细胞因子。 TGF-β通常以与潜伏期相关肽（LAP）相关的潜在形式发现。该潜在复合物可与潜在TGFβ结合蛋白（LTBP）缔合以产生大的潜在形式。在活化的FOXP3 +调节性T细胞（Tregs）的表面还发现了潜在的TGF-β，但尚不清楚它如何锚定在细胞膜上。我们表明，GARP或LRRC32，一种功能未知的富含亮氨酸的重复分子，对于将TGF-β束缚到细胞表面至关重要。我们证明血小板和活化的Tregs在其膜上共表达潜在的TGF-β和GARP。用siRNA敲低GARP mRNA可以阻止活化Tregs上的表面潜在TGF-β表达，而重组潜在TGF-β1可以直接与GARP结合。共聚焦显微镜和免疫沉淀强烈支持它们的相互作用。 TGF-β在Tregs上的作用似乎具有双重功能，既可用于Treg介导的抑制作用，又可用于感染耐受机制。

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  • 作者

    Dat Q. Tran; John Andersson; Rui Wang; Heather Ramsey; Derya Unutmaz; Ethan M. Shevach;

  • 作者单位

    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Department of Microbiology, New York University School of Medicine, New York, NY 10016;

    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

    Department of Microbiology, New York University School of Medicine, New York, NY 10016;

    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;

  • 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

    transforming growth factor beta; Tregs; latency-associated peptide;

    机译：转化生长因子β;茶渣;潜伏期相关肽;

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