Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Cell Rep. 2018 Jan 16;22(3):653-665. doi: 10.1016/j.celrep.2017.12.068.
A balance between Th17 and regulatory T (Treg) cells is critical for immune homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid-induced kinase 1 (SGK1) is critical for the development and function of Th17 cells. Here, we show that SGK1 restrains the function of Treg cells and reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to protection against autoimmunity and enhances self-tolerance by promoting Treg cell development and disarming Th17 cells. Treg cell-specific deletion of SGK1 results in enhanced Treg cell-suppressive function through preventing Foxo1 out of the nucleus, thereby promoting Foxp3 expression by binding to Foxp3 CNS1 region. Furthermore, our data suggest that SGK1 also plays a critical role in IL-23R-mediated inhibition of Treg and development of Th17 cells. Therefore, we demonstrate that SGK1 functions as a pivotal node in regulating the reciprocal development of pro-inflammatory Th17 and Foxp3 Treg cells during autoimmune tissue inflammation.
Th17 细胞和调节性 T（Treg）细胞之间的平衡对于免疫稳态和耐受至关重要。我们之前的工作表明，血清和糖皮质激素诱导激酶 1（SGK1）对于 Th17 细胞的发育和功能至关重要。在这里，我们表明 SGK1 抑制 Treg 细胞的功能，并通过反向调节 Th17/Treg 平衡来调节其发育。SGK1 缺陷可通过促进 Treg 细胞的发育和削弱 Th17 细胞来防止自身免疫并增强自身耐受。Treg 细胞特异性敲除 SGK1 通过阻止 Foxo1 出核来增强 Treg 细胞的抑制功能，从而通过与 Foxp3 CNS1 区域结合来促进 Foxp3 的表达。此外，我们的数据表明 SGK1 还在 IL-23R 介导的 Treg 抑制和 Th17 细胞发育中发挥关键作用。因此，我们证明 SGK1 在自身免疫性组织炎症期间作为调节促炎 Th17 和 Foxp3 Treg 细胞相互发育的关键节点发挥作用。
