在新诊断的 1 型糖尿病患儿和自身抗体阳性的高危患儿中,循环滤泡和常规 FOXP3 Treg 细胞上 PD-1 表达减少。
Reduced PD-1 expression on circulating follicular and conventional FOXP3 Treg cells in children with new onset type 1 diabetes and autoantibody-positive at-risk children.
机构信息
Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute, Milan, Italy; IRCCS Istituto tumori "G.Paolo II" of Bari, Bari, Italy.
出版信息
Clin Immunol. 2020 Feb;211:108319. doi: 10.1016/j.clim.2019.108319. Epub 2019 Nov 30.
Autoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular regulatory T (Treg) cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5) and conventional (CXCR5) Treg cells in the blood of children with new-onset T1D, and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls. Blood follicular and conventional Treg cells were higher in frequency in children with new onset T1D, but expressed reduced amounts of PD-1 as compared to AAb-negative children. Interestingly, the proportion of circulating FOXP3 Tregs expressing PD-1 was also reduced in AAb-positive at-risk children as compared to AAb-negative controls, suggesting its potential use as a biomarker of disease progression. Follicular Treg cells were reduced in frequency in the spleens of prediabetic NOD mice as they became older and turned diabetic. Interestingly, PD-1 expression declined also on circulating follicular and conventional Treg cells in prediabetic NOD mice as they aged. Together, these findings show that the frequency of circulating follicular and conventional Treg cells and their levels of PD-1 change with disease progression in children at-risk for developing T1D and in NOD mice.
自身抗体 (AAbs) 是 1 型糖尿病 (T1D) 的标志。先前已经在 1 型糖尿病 (T1D) 患者中记录了滤泡辅助 (Tfh) T 细胞的频率和表型的改变,但负责抑制 AAb 发育的滤泡调节性 T (Treg) 细胞的贡献尚不清楚。在这里,我们研究了新诊断的 T1D 儿童、有发展为 T1D 风险的儿童 (AAb 阳性) 以及与 AAb 阴性对照组的血液中滤泡 (CXCR5) 和常规 (CXCR5) Treg 细胞的频率和激活状态。与 AAb 阴性儿童相比,新诊断的 T1D 儿童的血液滤泡和常规 Treg 细胞的频率更高,但表达的 PD-1 量减少。有趣的是,与 AAb 阴性对照组相比,AAb 阳性高危儿童循环中的 FOXP3 Treg 表达 PD-1 的比例也降低,表明其可能作为疾病进展的生物标志物。随着年龄的增长和糖尿病的发生,糖尿病前期 NOD 小鼠的脾脏中滤泡 Treg 细胞的频率减少。有趣的是,随着年龄的增长,糖尿病前期 NOD 小鼠循环中的滤泡和常规 Treg 细胞上 PD-1 的表达也下降。总之,这些发现表明,在有发展为 T1D 风险的儿童和 NOD 小鼠中,循环滤泡和常规 Treg 细胞的频率及其 PD-1 水平随着疾病的进展而变化。