The BMP Pathway Participates in Human Naive CD4+ T Cell Activation and Homeostasis.
The BMP Pathway Participates in Human Naive CD4+ T Cell Activation and Homeostasis.
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BMP途径参与人天真的CD4+ T细胞激活和稳态。
DOI：
10.1371/journal.pone.0131453
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Varas A
中科院分区：
文献类型：
--
作者：
Martínez VG;Sacedón R;Hidalgo L;Valencia J;Fernández-Sevilla LM;Hernández-López C;Vicente A;Varas A
骨形态发生蛋白（Bone Morphogenetic Proteins, BMPs）是TGF-β超家族的一组分泌因子。在许多免疫细胞类型中的不同作用中，BMP已知调节胸腺内T细胞的发育，尽管BMP信号在人类成熟T细胞中的作用仍然难以捉摸。在这项研究中，我们证明了规范的BMP信号在调节人类初始CD4+ T细胞群的大小和功能的两个关键事件中是必要的：激活和稳态。经TCR刺激后，初始CD4+ T细胞上调BMP配体的表达，触发CD25+细胞中典型的BMP信号传导。阻断BMP信号主要通过调节IL-2来严重损害激活后的CD4+ T细胞增殖，因为在抑制BMP信号传导后，加入IL-2可以恢复正常的T细胞扩增。同样，典型BMP通路的激活对于维持细胞存活和IL-7诱导的稳态增殖都是必需的，IL-7是T细胞稳态的关键因子。此外，在缺乏BMP信号的情况下，IL-7触发的两个T细胞稳态关键受体CXCR4和CCR9的上调也被取消。总之，我们描述了典型BMP信号在人类初始CD4+ T细胞激活和体内平衡中的重要作用，这可能对临床应用有价值。
Bone Morphogenetic Proteins (BMPs) form a group of secreted factors that belongs to the TGF-β superfamily. Among different roles in a number of immune cell types, BMPs are known to regulate T cell development within the thymus, although the role of BMP signaling in human mature T cells remains elusive. In this study, we demonstrate that canonical BMP signaling is necessary during two critical events that regulate the size and function of human naive CD4+ T cell population: activation and homeostasis. Upon stimulation via TCR, naive CD4+ T cells upregulate the expression of BMP ligands triggering canonical BMP signaling in CD25+ cells. Blockade of BMP signaling severely impairs CD4+ T cell proliferation after activation mainly through regulation of IL-2, since the addition of this cytokine recuperates normal T cell expansion after inhibition of BMP signaling. Similarly, activation of canonical BMP pathway is required for both the maintenance of cell survival and the homeostatic proliferation induced by IL-7, a key factor for T cell homeostasis. Moreover, upregulation of two critical receptors for T cell homeostasis, CXCR4 and CCR9, triggered by IL-7 is also abrogated in the absence of BMP signaling. Collectively, we describe important roles of the canonical BMP signaling in human naive CD4+ T cell activation and homeostasis that could be valuable for clinical application.
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DOI：
10.4161/cc.27118
发表时间：
2014
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Hager-Theodorides AL;Ross SE;Sahni H;Mishina Y;Furmanski AL;Crompton T
通讯作者：
Crompton T
影响因子：
4.8
作者：
Nohe, A;Hassel, S;Knaus, P
通讯作者：
Knaus, P
影响因子：
5.3
作者：
Hartung, Anke;Bitton-Worms, Keren;Knaus, Petra
通讯作者：
Knaus, Petra
影响因子：
5.4
作者：
Martinez, Victor G.;Hidalgo, Laura;Varas, Alberto
通讯作者：
Varas, Alberto
影响因子：
5.2
作者：
Lee, Min Young;Lim, Hyun Woo;Han, Ho Jae
通讯作者：
Han, Ho Jae