Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida 33136.
Cold Spring Harb Perspect Biol. 2018 Mar 1;10(3):a028597. doi: 10.1101/cshperspect.a028597.
Cytokine signaling is indispensable for regulatory T-cell (Treg) development in the thymus, and also influences the homeostasis, phenotypic diversity, and function of Tregs in the periphery. Because Tregs are required for establishment and maintenance of immunological self-tolerance, investigating the role of cytokines in Treg biology carries therapeutic potential in the context of autoimmune disease. This review discusses the potent and diverse influences of interleukin (IL)-2 signaling on the Treg compartment, an area of knowledge that has led to the use of low-dose IL-2 as a therapy to reregulate autoaggressive immune responses. Evidence suggesting Treg-specific impacts of the cytokines transforming growth factor β (TGF-β), IL-7, thymic stromal lymphopoietin (TSLP), IL-15, and IL-33 is also presented. Finally, we consider the technical challenges and knowledge limitations that must be overcome to bring other cytokine-based, Treg-targeted therapies into clinical use.
细胞因子信号对于调节性 T 细胞（Treg）在胸腺中的发育是必不可少的，它也影响 Treg 在周围组织中的稳态、表型多样性和功能。由于 Treg 对于建立和维持免疫耐受是必需的，因此研究细胞因子在 Treg 生物学中的作用在自身免疫性疾病的背景下具有治疗潜力。这篇综述讨论了白细胞介素（IL）-2 信号对 Treg 区室的强大而多样的影响，这一知识领域导致了使用低剂量 IL-2 作为重新调节自身免疫反应的治疗方法。还提出了证据表明细胞因子转化生长因子β（TGF-β）、IL-7、胸腺基质淋巴细胞生成素（TSLP）、IL-15 和 IL-33 对 Treg 具有特异性影响。最后，我们考虑了必须克服的技术挑战和知识限制，以使其他基于细胞因子的、针对 Treg 的治疗方法进入临床应用。
