Qian Jinxiu, Yu Liuchunyang, Tian Meng, Li Xiaoyu, Bai Xiuyun, Yang Jue, Deng Rongjun, Liu Qiqiong, Lyu Aiping, Xiao Cheng, Liu Yuanyan
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hongkong, China.
Cell Death Discov. 2026 Feb 3;12(1):90. doi: 10.1038/s41420-026-02946-x.
Regulatory T (Treg) cells perform immunosuppressive functions in rapid response to genetic and environmental stress for maintaining the immune balance, which play a physiological role in preventing autoimmune and inflammatory diseases. Given the highly dynamic and reversible nature of small ubiquitin-like modifier (SUMO) modification, along with the predominant nuclear localization of SUMO paralogs and their associated enzymes, SUMOylation is essential for the flexible regulation of key nuclear processes in Treg cells, such as membraneless organelle formation, genome integrity, and cell cycle progression. Notably, SUMO:SUMO-interacting motif (SIM) interactions facilitate the formation of regulatory complexes that govern cellular processes, and enable crosstalk with other post-translational modifications (PTMs), particularly ubiquitination, phosphorylation, acetylation, and methylation, which are globally harnessed by Treg cells in various contexts to regulate key processes of protein stability, signaling pathways, transcriptional reprogramming, and epigenetic modifications, thereby fine-tuning their immune-regulatory responses. This review explores the multifaceted roles of SUMOylation in Treg cell biology, emphasizing its influence on differentiation, maturation, transcriptional and epigenetic regulation, and metabolic reprogramming. By delineating these pathways, we aim to uncover how dysregulation of SUMOylation may be destined to Treg cells mediated immune disorders, providing a foundation for therapeutic interventions.
调节性T（Treg）细胞在对遗传和环境应激的快速反应中发挥免疫抑制功能，以维持免疫平衡，这在预防自身免疫性疾病和炎症性疾病中发挥着生理作用。鉴于小泛素样修饰物（SUMO）修饰具有高度动态和可逆的性质，以及SUMO旁系同源物及其相关酶主要定位于细胞核，SUMO化对于灵活调节Treg细胞中的关键核过程至关重要，如无膜细胞器形成、基因组完整性和细胞周期进程。值得注意的是，SUMO：SUMO相互作用基序（SIM）相互作用促进了调控细胞过程的复合物的形成，并能够与其他翻译后修饰（PTM）发生串扰，特别是泛素化、磷酸化、乙酰化和甲基化，Treg细胞在各种情况下广泛利用这些修饰来调节蛋白质稳定性、信号通路、转录重编程和表观遗传修饰等关键过程，从而微调其免疫调节反应。本综述探讨了SUMO化在Treg细胞生物学中的多方面作用，强调其对分化、成熟、转录和表观遗传调控以及代谢重编程的影响。通过描绘这些途径，我们旨在揭示SUMO化失调如何可能导致Treg细胞介导的免疫紊乱，为治疗干预提供基础。
