Bioscience Immunology, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Front Immunol. 2022 Jun 30;13:932485. doi: 10.3389/fimmu.2022.932485. eCollection 2022.
CD4CD25Foxp3 regulatory T-cells (Tregs) are functionally characterized for their ability to suppress the activation of multiple immune cell types and are indispensable for maintaining immune homeostasis and tolerance. Disruption of this intrinsic brake system assessed by loss of suppressive capacity, cell numbers, and Foxp3 expression, leads to uncontrolled immune responses and tissue damage. The conversion of Tregs to a pathogenic pro-inflammatory phenotype is widely observed in immune mediated diseases. However, the molecular mechanisms that underpin the control of Treg stability and suppressive capacity are incompletely understood. This review summarizes the concepts of T cell stability and T cell plasticity highlighting underlying mechanisms including translational and epigenetic regulators that may enable translation to new therapeutic strategies. Our enhanced understanding of molecular mechanism controlling Tregs will have important implications into immune homeostasis and therapeutic potential for the treatment of immune-mediated diseases.
CD4CD25Foxp3 调节性 T 细胞（Tregs）的功能特征是其能够抑制多种免疫细胞类型的激活，对于维持免疫稳态和耐受是不可或缺的。通过抑制能力丧失、细胞数量减少和 Foxp3 表达降低来评估这种内在制动系统的破坏，会导致免疫反应失控和组织损伤。在免疫介导的疾病中，广泛观察到 Tregs 向致病性促炎表型的转化。然而，支持 Treg 稳定性和抑制能力控制的分子机制尚不完全清楚。这篇综述总结了 T 细胞稳定性和 T 细胞可塑性的概念，强调了包括翻译和表观遗传调节剂在内的潜在机制，这些机制可能为新的治疗策略提供了可能。我们对控制 Tregs 的分子机制的理解的提高，将对免疫稳态和治疗免疫介导疾病的治疗潜力具有重要意义。
