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Paper Reading 01 Hao Shi, Chaohong Liu, Haiyan Tan Hongbo Chi et al. Immunity IL-2-STAT5 pathway controlling the homeostasis and function of Treg cellshas been proved before, this is supported by studies that claimed IL2 and STAT5could maintain the expression and stability of Foxp3, p-STAT5+ Treg cell subpopulation displayed highly suppressive function in response to autoreactiveT cells. Meanwhile another study showed Tregs could adapt to low IL-2 for the activation of STAT5 signaling. But how Treg utilizes the limited IL2 to achieve STAT5 activation still unknown. In this article, authors performed a small-scale kinase inhibitor screening in IL2 stimulated Treg cells and identified serine/threonine kinases Mst1 and Mst2 as key regulators of IL2-STAT5 signaling in Treg cells. This is supported by Mst1/Mst2 deficient Treg cell causes fatal auto-immune disease in mice model. And transcriptome analysis revealed deletion of Mst1/Mst2 in Treg would downregulate IL-2 mediated gene and STAT5 activation. In addition, Mst1/Mst2 deficient Treg cells showed defective survival and expansion upon IL-2 stimulation. For the mechanism, the authors uncovered Mst1 interacts with DOCK-LRCHs complex to regulate Treg migration, loss of Mst1/Mst2 limits Treg cells to enter the T cell zone ofsecondary lymphoid organs and access to IL-2 for the phosphorylate of STAT5 and cell survival. https://www./science/article/pii/S1074761318304758?via%3Dihub 02 Shaojun Xing, Kexin Gai et al. J. Exp. Med. 2019 Transcription factors Tcf1 and Lef1 have been wildly studied in T cell development and differentiation. such as promoting Th2 and Tfh but repressing Th1 and Th17 cells in mature CD4+ T cells, and establishingCD8+ T cell identity. These two factors have been also identified as Treg signaturegenes that are under expressed in Treg compared with T conv cells, and considered to be among Treg–down signature genes by Dr Benoist and his colleagues in 2012.However the specific function of Tcf1 and Tef1 in Treg cells still unknown. In this article, authors revealed the essential role of Tfc1 and Tef1 in sustaining the Treg suppressive functions and immune homeostasis. They found Tcf1/Lef1-deficient Treg cells were much less effective in preventing inflammation in vivo in both acute and chronic colitis models than WT Treg cells. And specific ablation of Tcf1 and Lef1 in Treg cells resulted in spontaneous autoimmunity with aging. Through RNAseq analysis they found massive downregulated genes involved in Treg suppressive function like Gpr83, ikzf4, Gzmb. Further to explore the mechanism, they performed ChIP-Seq assay of Treg cells, WT or Tcf1/Lef1 deficient CD4+ T cells,and demonstrated that Tcf1 and Lef1 function as critical components in aportion of Foxp3 complexes then cooperate with Foxp3 to regulate specific geneexpression in Treg cells. http://jem./content/216/4/847END |
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