Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Nat Immunol. 2012 May;13(5):481-90. doi: 10.1038/ni.2267.
The maintenance of immune homeostasis requires regulatory T cells (Treg cells). Here we found that Treg cell–specific ablation of Ubc13, a Lys63 (K63)-specific ubiquitin-conjugating enzyme, caused aberrant T cell activation and autoimmunity. Although Ubc13 deficiency did not affect the survival of Treg cells or expression of the transcription factor Foxp3, it impaired the in vivo suppressive function of Treg cells and rendered them sensitive to the acquisition of T helper type 1 (TH1) cell– and interleukin 17 (IL-17)-producing helper T (TH17) cell–like effector phenotypes. This function of Ubc13 involved its downstream target, the kinase IKK. The Ubc13-IKK signaling axis controlled the expression of specific Treg cell effector molecules, including IL-10 and SOCS1. Collectively, our findings suggest that the Ubc13-IKK signaling axis regulates the molecular program that maintains Treg cell function and prevents Treg cells from acquiring inflammatory phenotypes.
维持免疫稳态需要调节性 T 细胞（Treg 细胞）。在这里，我们发现 Ubc13（一种赖氨酸 63（K63）特异性泛素连接酶）在 Treg 细胞中的特异性缺失会导致异常的 T 细胞激活和自身免疫。尽管 Ubc13 缺乏并不影响 Treg 细胞的存活或转录因子 Foxp3 的表达，但它会损害 Treg 细胞在体内的抑制功能，使它们容易获得 T 辅助细胞 1（TH1）和白细胞介素 17（IL-17）产生辅助性 T（TH17）细胞样效应表型。Ubc13 的这种功能涉及其下游靶标激酶 IKK。Ubc13-IKK 信号轴控制着特定 Treg 细胞效应分子的表达，包括 IL-10 和 SOCS1。总之，我们的研究结果表明，Ubc13-IKK 信号轴调节维持 Treg 细胞功能并防止 Treg 细胞获得炎症表型的分子程序。
