Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Eur J Immunol. 2021 Sep;51(9):2137-2150. doi: 10.1002/eji.202048794. Epub 2021 Aug 15.
Regulatory T (Treg) cells and T helper type 17 (Th17) cells play important roles in adaptive immune responses, antagonizing each other in immune disorders. Th17/Treg balance is critical to maintaining the immune homeostasis of human bodies and is tightly regulated under healthy conditions. The transcription factors that are required for driving Th17 and Treg cell lineages differentiation respectively, RORγt and FOXP3 are tightly regulated under different tissue microenvironment, especially the transcriptional induction, posttranslational modifications, and dynamic enzymatic cofactors binding. The imbalance caused by alteration of the quantity or properties of RORγt Th17 or FOXP3 Treg can contribute to inflammatory disorders in humans. Restoring Th17/Treg balance by modifying the enzymatic activities of RORγt and FOXP3 binding partners may be therapeutically applied to treat severe immune disorders. In this review, we focus on the transcriptional and posttranslational regulations of Th17/Treg balance, immune disorders caused by Th17/Treg imbalance, and new therapeutic strategies for restoring immune homeostasis.
调节性 T (Treg) 细胞和辅助性 T 细胞 17 型 (Th17) 在适应性免疫反应中发挥重要作用，在免疫紊乱中相互拮抗。Th17/Treg 平衡对于维持人体免疫稳态至关重要，并在健康条件下受到严格调节。分别驱动 Th17 和 Treg 细胞谱系分化所必需的转录因子 RORγt 和 FOXP3 在不同的组织微环境下受到严格调节，特别是转录诱导、翻译后修饰和动态酶共因子结合。RORγt Th17 或 FOXP3 Treg 的数量或性质的改变所导致的失衡可能导致人类发生炎症性疾病。通过修饰 RORγt 和 FOXP3 结合伙伴的酶活性来恢复 Th17/Treg 平衡，可能具有治疗严重免疫紊乱的应用价值。在这篇综述中，我们重点关注 Th17/Treg 平衡的转录和翻译后调控、由 Th17/Treg 失衡引起的免疫紊乱，以及恢复免疫稳态的新治疗策略。
