Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells

摘要

The homeostatic balance between effector T cells and regulatory T cells(Tregs)is crucial for adaptive immunity;however,epigenetic programs that inhibit phosphorylation to regulate Treg development,peripheral expression,and suppressive activity are elusive.Here,we found that the Ssu72 phosphatase is activated by various T-cell receptor signaling pathways,including the T-cell receptor and IL-2R pathways,and localizes at the cell membrane.Deletion of Ssu72 in T cells disrupts CD4+T-cell differentiation into Tregs in the periphery via the production of high levels of the effector cytokines IL-2 and IFNγ,which induce CD4+T-cell activation and differentiation into effector cell lineages.We also found a close correlation between downregulation of Ssu72 and severe defects in mucosal tolerance in patients.Interestingly,Ssu72 forms a complex with PLCγ1,which is an essential effector molecule for T-cell receptor signaling as well as Treg development and function.Ssu72 deficiency impairs PLCγ1 downstream signaling and results in failure of Foxp3 induction.Thus,our studies show that the Ssu72-mediated cytokine response coordinates the differentiation and function of Treg cells in the periphery.