Lkb1 maintains Treg cell lineage identity.
Di WuYuechen LuoWei GuoQing NiuTing XueFei YangXiaolei SunSong ChenYuanyuan LiuJingru LiuZhina SunChunxiao ZhaoHuifang HuangFang LiaoZhongchao HanDongming ZhouYongguang YangGuogang XuTao ChengXiaoming FengPublished in: Nature communications (2017)
Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg 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 Treg cell lineage identity.
Keyphrases
- regulatory t cells
- poor prognosis
- single cell
- early onset
- induced apoptosis
- binding protein
- stem cells
- public health
- transcription factor
- oxidative stress
- long non coding rna
- mesenchymal stem cells
- blood brain barrier
- immune response
- transforming growth factor
- epithelial mesenchymal transition
- signaling pathway
- metabolic syndrome
- late onset
- cell proliferation
- adipose tissue
- pi k akt