Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease
Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease
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DOI：
10.1016/s1074-7613(00)80170-3
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发表时间：
2000-02-01
期刊：
影响因子：
32.4
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Gorelik, L;Flavell, RA
在小鼠中对转化生长因子β1进行靶向突变表明，转化生长因子β1是免疫稳态的关键负调控因子之一，因为其缺失会导致自身靶向免疫反应的激活。然而，由于转化生长因子β具有高度多效性，且大多数细胞类型上都存在转化生长因子β受体，其在免疫稳态调节中的生物学作用尚未明确。为了将转化生长因子β的作用局限于单一细胞类型，我们开发了一种转基因方法来消除关键免疫细胞中对转化生长因子β的反应。具体而言，我们在T细胞特异性启动子下表达了一种显性负性的Ⅱ型转化生长因子β受体，并创建了一个在T细胞中特异性阻断转化生长因子β信号传导的小鼠模型。利用这个转基因模型，我们表明T细胞稳态需要T细胞中的转化生长因子β信号传导。
Targeted mutation of TGF beta 1 in mice demonstrated that TGF beta 1 is one of the key negative regulators of immune homeostasis, as its absence leads to activation of a self-targeted immune response. Nevertheless, because of the highly pleiotropic properties of TGF beta and the presence of TGF beta receptors on most cell types, its biologic role in the regulation of immune homeostasis is not yet understood. To limit the consequences of TGF beta effects to a single cell type, we developed a transgenic approach to abrogate the TGF beta response in key immune cells. Specifically, we expressed a dominant-negative TGF beta receptor type II under a T cell-specific promoter and created a mouse model where signaling by TGF beta is blocked specifically in T cells. Using this transgenic model, we show that T cell homeostasis requires TGF beta signaling in T cells.