Regulatory T (T_reg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve T_reg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains T_reg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in T_reg cells but not in conventional T cells. Mice with T_reg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most T_reg cells. Lkb1 stabilizes Foxp3 expression by preventing STAT4-mediated methylation of the conserved noncoding sequence 2 (CNS2) in the Foxp3 locus. Independent of maintaining Foxp3 expression, Lkb1 programs the expression of a wide spectrum of immunosuppressive genes, through mechanisms involving the augmentation of TGF-β signalling. These findings identify a critical function of Lkb1 in maintaining T_reg cell lineage identity.

中文翻译：

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Lkb1保持Treg细胞谱系身份。

调节性T（T _reg）细胞是一种独特的T细胞谱系，其特征是持续的Foxp3表达和有效的抑制功能，但保留T _reg谱系特有特征的上游显性因子大多未知。在这里，我们显示Lkb1通过稳定Foxp3表达和执行抑制功能来维持T _reg细胞谱系同一性。在T细胞受体（TCR）刺激下，Lreg蛋白在T _reg细胞中表达上调，而在常规T细胞中则不上调。具有T _reg细胞特异性Lkb1缺失的小鼠发展为致命的早期发作的自身免疫病，大多数T _reg中均未表达Foxp3细胞。Lkb1通过阻止Foxp3基因座中保守的非编码序列2（CNS2）的STAT4介导的甲基化来稳定Foxp3的表达。独立于维持Foxp3表达，Lkb1通过涉及TGF-β信号增强的机制来编程表达广泛的免疫抑制基因。这些发现确定了Lkb1在维持T _reg细胞谱系同一性中的关键功能。