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首页> 外文期刊>Nature immunology >Control of PI(3) kinase in T-reg cells maintains homeostasis and lineage stability
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Control of PI(3) kinase in T-reg cells maintains homeostasis and lineage stability

机译:T reg细胞中PI(3)激酶的控制保持体内稳态和谱系稳定性

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摘要

Foxp3(+) regulatory T cells (T-reg cells) are required for immunological homeostasis. One notable distinction between conventional T cells (T-conv cells) and T-reg cells is differences in the activity of phosphatidylinositol-3-OH kinase (PI(3)K); only T-conv cells downregulate PTEN, the main negative regulator of PI(3)K, upon activation. Here we found that control of PI(3)K in T-reg cells was essential for lineage homeostasis and stability. Mice lacking Pten in T-reg cells developed an autoimmune-lymphoproliferative disease characterized by excessive T helper type 1 (T(H)1) responses and B cell activation. Diminished control of PI(3)K activity in T-reg cells led to reduced expression of the interleukin-2 (IL-2) receptor alpha subunit CD25, accumulation of Foxp3(+) CD25(-) cells and, ultimately, loss of expression of the transcription factor Foxp3 in these cells. Collectively, our data demonstrate that control of PI(3)K signaling by PTEN in T-reg cells is critical for maintaining their homeostasis, function and stability.
机译:免疫稳态需要Foxp3(+)调节性T细胞(T-reg细胞)。传统T细胞(T-conv细胞)和T-reg细胞之间的一个显着区别是磷脂酰肌醇-3-OH激酶(PI(3)K)的活性不同。只有T-conv细胞在激活后下调PTEN(PI(3)K的主要负调节剂)。在这里,我们发现在T-reg细胞中控制PI(3)K对于谱系稳态和稳定性至关重要。 T-reg细胞中缺乏Pten的小鼠发展出一种自身免疫性淋巴增生性疾病,其特征是过度的1型T辅助细胞(T(H)1)反应和B细胞活化。在T-reg细胞中PI(3)K活性的减弱控制导致白介素2(IL-2)受体α亚基CD25的表达减少,Foxp3(+)CD25(-)细胞的积累,最终导致丧失这些细胞中转录因子Foxp3的表达。总的来说,我们的数据表明,通过TTEN细胞中PTEN对PI(3)K信号的控制对于维持其稳态,功能和稳定性至关重要。

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