Longgang ENT Hospital and Affiliated ENT Institute of Shenzhen University, Shenzhen, China.
Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China; Department of allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, China.
Immunol Lett. 2019 Jun;210:47-54. doi: 10.1016/j.imlet.2019.04.005. Epub 2019 Apr 25.
Dysfunction of immune regulatory cells has been recognized in a variety of immune diseases; the underlying mechanism remains to be further investigated. This study aims to investigate the critical role of Toll-like receptor (TLR) signal in the maintenance of function of regulatory T cells (Tregs). In this study, Tregs were isolated from patients with allergic rhinitis (AR) and healthy control (HC) subjects. The role of TLR signal in the maintenance of Treg's function was tested with experiments of cell culture and an AR mouse model. We observed that the immune suppressive function of AR Treg (Tregs isolated from AR patients) was impaired, although the number of peripheral AR Treg was comparable with HC Treg. Expression of transforming growth factor (TGF)-β was lower in AR Tregs than that in HC Tregs that was positively correlated with expression of Mal in Tregs; the latter was lower in AR Tregs as compared to HC Tregs. TGF-β mRNA in Tregs decayed spontaneously in the culture. Activation of Mal counteracted TGF-β decay and maintained the Treg's immune regulatory function. Mal bound Tristetraprolin (TTP) to prevent TTP from inducing TGF-β mRNA decay. Absence of TLR signals resulted in Treg dysfunctional and worsened experimental AR response in a murine model. In conclusion, TLR signal is required in the maintenance of Treg function. Absence of TLR signal may result in Treg dysfunction and immune intolerance.
免疫调节细胞功能障碍已在多种免疫性疾病中得到证实；其潜在的机制仍有待进一步研究。本研究旨在探讨 Toll 样受体（TLR）信号在维持调节性 T 细胞（Tregs）功能中的关键作用。在这项研究中，我们从变应性鼻炎（AR）患者和健康对照（HC）受试者中分离出 Tregs。通过细胞培养实验和 AR 小鼠模型来测试 TLR 信号在维持 Treg 功能中的作用。我们观察到，尽管外周 AR Treg 的数量与 HC Treg 相当，但 AR Treg（从 AR 患者中分离出的 Treg）的免疫抑制功能受损。AR Tregs 中的转化生长因子（TGF）-β表达较低，与 Tregs 中 Mal 的表达呈正相关；而 AR Tregs 中的 Mal 表达低于 HC Tregs。Tregs 中的 TGF-β mRNA 在培养中自发降解。Mal 的激活可阻止 TGF-β 的降解，维持 Treg 的免疫调节功能。Mal 结合 Tristetraprolin（TTP）以防止 TTP 诱导 TGF-β mRNA 降解。TLR 信号的缺失导致 Treg 功能障碍，并在小鼠模型中加重实验性 AR 反应。总之，TLR 信号对于维持 Treg 功能是必需的。TLR 信号的缺失可能导致 Treg 功能障碍和免疫耐受。
