Apostolidis Sokratis A, Rodríguez-Rodríguez Noé, Suárez-Fueyo Abel, Dioufa Nikolina, Ozcan Esra, Crispín José C, Tsokos Maria G, Tsokos George C
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Nat Immunol. 2016 May;17(5):556-64. doi: 10.1038/ni.3390. Epub 2016 Mar 14.
Homeostasis of the immune system depends on the proper function of regulatory T cells (T(reg) cells). Compromised suppressive activity of T(reg) cells leads to autoimmune disease and graft rejection and promotes anti-tumor immunity. Here we report a previously unrecognized requirement for the serine-threonine phosphatase PP2A in the function of T(reg) cells. T(reg) cells exhibited high PP2A activity, and T(reg) cell-specific ablation of the PP2A complex resulted in a severe, multi-organ, lymphoproliferative autoimmune disorder. Mass spectrometry revealed that PP2A associated with components of the mTOR metabolic-checkpoint kinase pathway and suppressed the activity of the mTORC1 complex. In the absence of PP2A, T(reg) cells altered their metabolic and cytokine profile and were unable to suppress effector immune responses. Therefore, PP2A is required for the function of T(reg) cells and the prevention of autoimmunity.
免疫系统的稳态依赖于调节性T细胞（Treg细胞）的正常功能。Treg细胞抑制活性受损会导致自身免疫性疾病和移植排斥反应，并促进抗肿瘤免疫。在此，我们报告了丝氨酸-苏氨酸磷酸酶PP2A在Treg细胞功能中一个此前未被认识到的需求。Treg细胞表现出高PP2A活性，PP2A复合物在Treg细胞中的特异性缺失导致严重的多器官淋巴细胞增殖性自身免疫性疾病。质谱分析显示PP2A与mTOR代谢检查点激酶途径的成分相关联，并抑制mTORC1复合物的活性。在缺乏PP2A的情况下，Treg细胞改变了它们的代谢和细胞因子谱，并且无法抑制效应性免疫反应。因此，PP2A是Treg细胞功能和预防自身免疫所必需的。
