Genomic definition of multiple ex vivo regulatory T cell subphenotypes
Genomic definition of multiple ex vivo regulatory T cell subphenotypes
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DOI：
10.1073/pnas.1002006107
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发表时间：
2010-03-30
影响因子：
11.1
通讯作者：
Benoist, Christophe
中科院分区：
文献类型：
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作者：
Feuerer, Markus;Hill, Jonathan A.;Benoist, Christophe
表达Foxp3转录因子的调节性T（Treg）细胞对于淋巴稳态和对自身的免疫耐受是必不可少的。Treg细胞的其他非免疫功能，如控制脂肪组织中的代谢功能，也正在出现。Treg细胞主要来源于胸腺，但也可以通过体内暴露于低剂量抗原或稳态扩增或通过在体外存在TGF β的情况下活化而从常规T细胞引发。Treg细胞的特征在于部分但不完全由Foxp3控制的独特的转录签名。为了更好地了解Treg细胞中的转录控制，我们比较了来自不同来源或解剖位置的广泛Treg细胞的基因表达谱。通过不同方法产生的Treg细胞形成不同的亚表型，并且可通过转录物的特定组合来识别，其中没有一种转录物完全涵盖整个Treg标签。参与Treg细胞效应功能的分子、趋化因子受体和控制它们的转录因子在这些亚表型中表现出差异。事实证明，来自肠道的Treg细胞与体外暴露于TGF β引起的细胞不同，但它们类似于优先响应淋巴细胞减少症而产生的CD 103（+）Klrg 1（+）亚表型。
Regulatory T (Treg) cells that express the Foxp3 transcription factor are essential for lymphoid homeostasis and immune tolerance to self. Other nonimmunological functions of Treg cells, such as controlling metabolic function in adipose tissue, are also emerging. Treg cells originate primarily in the thymus, but can also be elicited from conventional T cells by in vivo exposure to low-dose antigen or homeostatic expansion or by activation in the presence of TGF beta in vitro. Treg cells are characterized by a distinct transcriptional signature controlled in part, but not solely, by Foxp3. For a better perspective on transcriptional control in Treg cells, we compared gene expression profiles of a broadpanel of Treg cells from various origins or anatomical locations. Treg cells generated by different means form different subphenotypes and were identifiable by particular combinations of transcripts, none of which fully encompassed the entire Treg signature. Molecules involved in Treg cell effector function, chemokine receptors, and the transcription factors that control them were differentially represented in these subphenotypes. Treg cells from the gut proved dissimilar to cells elicited by exposure to TGF beta in vitro, but instead they resembled a CD103(+)Klrg1(+) subphenotype preferentially generated in response to lymphopenia.