Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, R.O.C.
Division of Genetics and Metabolism, Children's Hospital of China Medical University, Taichung, Taiwan, R.O.C.
In Vivo. 2022 Sep-Oct;36(5):2083-2091. doi: 10.21873/invivo.12934.
BACKGROUND/AIM: The T cell's flexibility of the immune system to be regulated affects the onset of type 1 diabetes (T1D). However, the mechanisms of endoplasmic reticulum (ER) stress and inflammasome activation in the circulating CD3CD56 T cells of patients with T1D remain unclear. This study evaluated the role of CD3CD56 T cells in T1D and their correlations with ER stress, inflammasome activation and disease characteristics.
The frequency of circulating CD3CD56 T cells was determined using flow cytometry in healthy individuals and patients with T1D. Calnexin, NLR family pyrin domain containing 3 (NLRP3), ASC, caspase-1 (Casp1), cleaved caspase-3 (C-Casp3), and annexin V (AnnV) expression and propidium iodide staining in CD3/CD56 T cells were analyzed using flow cytometry.
The frequency of CD3CD56 T cells was reduced in patients with T1D relative to that in healthy individuals. In addition, high calnexin, NLRP3, ASC and Casp1 expression in CD3CD56 T cells was negatively correlated with the percentage of CD3CD56 T cells in patients with T1D.
ER stress, inflammasome activation, and a lower peripheral frequency of circulating CD3CD56 T cells might indicate disease progression and necessitate clinical T1D immunological self-tolerance monitoring.
背景/目的:免疫系统中 T 细胞的灵活性受到调节,这会影响 1 型糖尿病(T1D)的发病。然而,T1D 患者循环 CD3CD56 T 细胞中内质网(ER)应激和炎性体激活的机制尚不清楚。本研究评估了 CD3CD56 T 细胞在 T1D 中的作用及其与 ER 应激、炎性体激活和疾病特征的相关性。
采用流式细胞术检测健康个体和 T1D 患者循环 CD3CD56 T 细胞的频率。采用流式细胞术分析 CD3/CD56 T 细胞中钙网织蛋白、NLR 家族 pyrin 结构域包含 3(NLRP3)、ASC、半胱天冬酶-1(Casp1)、裂解的半胱天冬酶-3(C-Casp3)和膜联蛋白 V(AnnV)的表达和碘化丙啶染色。
与健康个体相比,T1D 患者 CD3CD56 T 细胞的频率降低。此外,CD3CD56 T 细胞中高钙网织蛋白、NLRP3、ASC 和 Casp1 表达与 T1D 患者 CD3CD56 T 细胞的百分比呈负相关。
ER 应激、炎性体激活以及外周循环 CD3CD56 T 细胞频率降低可能提示疾病进展,需要对 T1D 进行临床免疫自身耐受监测。