Regenerative Medicine Institute (REMEDI) at CÚRAM SFI Research Centre for Medical Devices, School of Medicine, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland.
Nephrology Department, Galway University Hospitals, Saolta University Healthcare Group, Galway, Ireland.
Front Immunol. 2023 Oct 20;14:1287465. doi: 10.3389/fimmu.2023.1287465. eCollection 2023.
Regulatory T cells (Treg) are known to be critical for the maintenance of immune homeostasis by suppressing the activation of auto- or allo-reactive effector T cells through a diverse repertoire of molecular mechanisms. Accordingly, therapeutic strategies aimed at enhancing Treg numbers or potency in the setting of autoimmunity and allogeneic transplants have been energetically pursued and are beginning to yield some encouraging outcomes in early phase clinical trials. Less well recognized from a translational perspective, however, has been the mounting body of evidence that Treg directly modulate most aspects of innate immune response under a range of different acute and chronic disease conditions. Recognizing this aspect of Treg immune modulatory function provides a bridge for the application of Treg-based therapies to common medical conditions in which organ and tissue damage is mediated primarily by inflammation involving myeloid cells (mononuclear phagocytes, granulocytes) and innate lymphocytes (NK cells, NKT cells, γδ T cells and ILCs). In this review, we comprehensively summarize pre-clinical and human research that has revealed diverse modulatory effects of Treg and specific Treg subpopulations on the range of innate immune cell types. In each case, we emphasize the key mechanistic insights and the evidence that Treg interactions with innate immune effectors can have significant impacts on disease severity or treatment. Finally, we discuss the opportunities and challenges that exist for the application of Treg-based therapeutic interventions to three globally impactful, inflammatory conditions: type 2 diabetes and its end-organ complications, ischemia reperfusion injury and atherosclerosis.
调节性 T 细胞（Treg）通过多种分子机制抑制自身或同种异体反应性效应 T 细胞的激活，从而被认为对维持免疫稳态至关重要。因此，在自身免疫和同种异体移植的背景下，旨在增强 Treg 数量或效力的治疗策略已被积极探索，并在早期临床试验中开始产生一些令人鼓舞的结果。然而，从转化的角度来看，人们对 Treg 直接调节多种不同急性和慢性疾病条件下固有免疫反应的大部分方面的证据认识不足。认识到 Treg 免疫调节功能的这一方面为将基于 Treg 的治疗应用于主要由涉及髓样细胞（单核吞噬细胞、粒细胞）和固有淋巴细胞（NK 细胞、NKT 细胞、γδ T 细胞和 ILCs）的炎症介导的器官和组织损伤的常见医疗条件提供了桥梁。在这篇综述中，我们全面总结了揭示 Treg 和特定 Treg 亚群对一系列固有免疫细胞类型的多种调节作用的临床前和人类研究。在每种情况下，我们都强调了关键的机制见解和证据，即 Treg 与固有免疫效应物的相互作用可以对疾病严重程度或治疗产生重大影响。最后，我们讨论了将基于 Treg 的治疗干预应用于三种具有全球影响力的炎症性疾病的机会和挑战：2 型糖尿病及其终末器官并发症、缺血再灌注损伤和动脉粥样硬化。
