Follicular regulatory T cells are associated with β-cell autoimmunity and the development of type 1 diabetes.
Follicular regulatory T cells are associated with β-cell autoimmunity and the development of type 1 diabetes.
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DOI：
10.1210/jc.2019-00093
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发表时间：
2019-05
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影响因子：
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通讯作者：
Xinyu Xu;Min Shen;Ruiling Zhao;Yun Cai;Hemin Jiang;Ziyang Shen;R. Gao;Kuanfeng Xu;Heng Chen-Heng-Ch
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文献类型：
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作者：
Xinyu Xu;Min Shen;Ruiling Zhao;Yun Cai;Hemin Jiang;Ziyang Shen;R. Gao;Kuanfeng Xu;Heng Chen-Heng-Ch
目的：滤泡调节性T（Tfr）细胞受损后，可增强滤泡辅助性T细胞（Tfh）的活性，导致自身反应性B细胞的扩增和自身抗体的产生。然而，Tfr细胞在1型糖尿病（T1 D）发病机制中的作用尚不清楚。方法通过研究T1 D患者、2型糖尿病患者（T2 D）、T1 D患者一级亲属（T1 D-FRs）和健康对照者，评价循环Tfr细胞的表达和功能变化。我们还研究了Tfr细胞对NOD小鼠和过继转移模型中疾病发展的影响。结果Tfr细胞在两组患者中均明显减少。但在T1 D和T2 D患者中，它们与空腹C肽（C-P）和血C肽曲线下面积（C-PAUC）的相关性不同。Tfr细胞频率与T1 D患者自身抗体阳性数及GAD抗体滴度相关。此外，Tfr细胞在随访1年后显著下降。我们还观察了Tfr细胞在四个T1 D患者与利妥昔单抗治疗。利妥昔单抗治疗后，3例患者CXCR 5 +PD-1+ Tfr细胞的频率降低，CXCR 5 +ICOS+ Tfr细胞的频率增加。我们还发现Tfr细胞与NOD小鼠和过继转移模型中糖尿病的发展相关。结论Tfr细胞缺陷可能参与了T1 D的发病过程。Tfr细胞治疗对T1 D具有潜在价值。这些细胞的调节可能是增强保护性免疫以抑制自身免疫性糖尿病。
OBJECTIVE Impaired follicular regulatory T (Tfr) cells enhance T follicular helper (Tfh) cells activity, resulting in the expansion of autoreactive B cells and autoantibody production. However, the role of Tfr cells in the pathogenesis of type 1 diabetes (T1D) is unclear. METHODS We evaluated the expression and changes in function of circulating Tfr cells by studying patients with T1D alongside those with type 2 diabetes(T2D), first-degree relatives of T1D patients (T1D-FRs) and healthy controls. We also investigated the effects of Tfr cells on disease development in NOD mice and in an adoptive transfer model. RESULTS Tfr cells were significantly decreased in both patient groups. However, they showed different correlations with fasting C-peptide (C-P) and the area under the curve of blood C-peptide (C-PAUC) in patients with T1D and T2D. The frequency of Tfr cells was associated with the number of positive autoantibodies and the titer of GAD autoantibody in T1D patients. Furthermore, Tfr cells decreased significantly after 1 year of follow-up. We also observed Tfr cells in four T1D patients treated with rituximab. After rituximab therapy, the frequency of CXCR5+PD-1+ Tfr cells was decreased and of CXCR5+ICOS+ Tfr cells was increased in three patients. We also found that Tfr cells were associated with the development of diabetes in NOD mice and an adoptive transfer model. CONCLUSIONS Tfr cell deficiency could be involved in the pathogenesis of T1D. Therapy with Tfr cells has potential value for T1D. Modulation of these cells may be enhance protective immunity to inhibit autoimmune diabetes.