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

Cellular & Molecular Immunology 2021年第6期18卷 1395-1411页

作者： 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 heounjeong go Chang-Woo Lee Research Institute Curogen TechnologySuwonSouth Korea Department of Molecular Cell Biology Samsung Medical CenterSungkyunkwan University School of MedicineSuwonSouth Korea MOGAM Institute for Biomedical Research GyeonggiSouth Korea Department of Pathology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea Asan Institute for Life Sciences Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea Department of Immunology Sungkyunkwan University School of MedicineSeoulSouth Korea Department of Cancer Biomedical Science Graduate School of Cancer Science and PolicyResearch InstituteNational Cancer CenterGyeonggiSouth Korea

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 ***,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 *** 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 *** also found a close correlation between downregulation of Ssu72 and severe defects in mucosal tolerance in ***,Ssu72 forms a complex with PLCγ1,which is an essential effector molecule for T-cell receptor signaling as well as Treg development and ***72 deficiency impairs PLCγ1 downstream signaling and results in failure of Foxp3 ***,our studies show that the Ssu72-mediated cytokine response coordinates the differentiation and function of Treg cells in the periphery.

关键词： Ssu72 Regulatory T cells FoxP3 T cell receptor Autoimmunity

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