Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells
- 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 IFN gamma, 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 PLC gamma 1, which is an essential effector molecule for T-cell receptor signaling as well as Treg development and function. Ssu72 deficiency impairs PLC gamma 1 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.
- Jin-Kwan Lee; Seo-Young Koo; Hye-Mi Nam; Jee-Boong Lee; Jiwon Ko; Kyung-Mo Kim; Eun-Ji Park; Tae Jin Kim; Ho Lee; 고현정; Chang-Woo Lee
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- Autoimmunity; FoxP3; Regulatory T cells; Ssu72; T cell receptor
- CELLULAR MOLECULAR IMMUNOLOGY
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