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有读书笔记有附件Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict

聚焦生物 添加于 2012-12-26 22:00 | 2514 次阅读 | 0 个评论

  •  作 者

    Samstein RM, Josefowicz SZ, Arvey A, Treuting PM, Rudensky AY

  •  摘 要

    Regulatory T (Treg) cells, whose differentiation and function are controlled by X chromosome-encoded transcription factor Foxp3, are generated in the thymus (tTreg) and extrathymically (peripheral, pTreg), and their deficiency results in fatal autoimmunity. Here, we demonstrate that a Foxp3 enhancer, conserved noncoding sequence 1 (CNS1), essential for pTreg but dispensable for tTreg cell generation, is present only in placental mammals. CNS1 is largely composed of mammalian-wide interspersed repeats (MIR) that have undergone retrotransposition during early mammalian radiation. During pregnancy, pTreg cells specific to a model paternal alloantigen were generated in a CNS1-dependent manner and accumulated in the placenta. Furthermore, when mated with allogeneic, but not syngeneic, males, CNS1-deficient females showed increased fetal resorption accompanied by increased immune cell infiltration and defective remodeling of spiral arteries. Our results suggest that, during evolution, a CNS1-dependent mechanism of extrathymic differentiation of Treg cells emerged in placental animals to enforce maternal-fetal tolerance.

  •  详细资料

    • 关键词: Animals; Enhancer Elements, Genetic; Female; Fetus/immunology; Forkhead Transcription Factors/genetics; Humans; *Immune Tolerance; Male; Mammals/genetics/*immunology; Mice; Opossums; Placenta/*cytology/*immunology; Pregnancy/*immunology; T-Lymphocytes, Regulatory/*immunology
    • 文献种类: Journal Article
    • 期刊名称: Cell
    • 期刊缩写: Cell
    • 期卷页: 2012年  第150卷 第1期 29-38页
    • 地址: Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
    • ISBN: 0092-8674

  • 学科领域 生物医药 » 生物学

  • 相关链接 DOI URL 

  •  附 件

    PDF附件Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict 

  •  聚焦生物 的文献笔记  订阅

    调节性T（Treg）细胞的分化和功能受到X染色质编码的转录因子Foxp3的调控，这种T细胞在胸腺（称为tTreg）和神经末梢区域（称为pTreg）形成，如果缺乏这些T细胞会导致致命的自身免疫。 我们证明了Foxp3增强子位于保守的非编码区1（CNS1），它们对于pTreg是必须的，但对于tTrep细胞的形成是非必须的，且这种增强子仅在胎 盘类哺乳动物中存在。CNS1主要是由野生型哺乳动物散在重复序列（MIR）组成，MIR在早期哺乳动物放射过程中经历逆转录转座(作用)。在怀孕过程 中，pTreg细胞对于父本异体抗原具有专一性，这种细胞在CNS1依赖过程中形成并在胎盘中积累。而且，当与同种基因而不是同系基因配对时，男性和 CNS-1缺陷型的女性表现出胚胎吸收增加的现象，并伴随免疫细胞渗透的增加和螺旋动脉的缺陷形成。我们的实验结果表明在进化过程中，Treg细胞胸腺外 分化的CNS-1依赖型机制出现在胎盘动物中从而增强母本-胎儿的耐受。
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