Shanghai Clinical Research Center for Tuberculosis, Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Shanghai Public Health Clinical Center, Shanghai, China.
J Immunol Res. 2021 Feb 11;2021:6625855. doi: 10.1155/2021/6625855. eCollection 2021.
-Catenin is a key molecule of canonical Wnt/-catenin pathway. Its roles and expression profiles in T cells of tuberculosis (TB) remain unclear. The aim of this study was to explore the role of -catenin in CD4 T cells and its expression characteristics in patients with pulmonary tuberculosis (PTB). In this study, CD4 T cell-specific -catenin conditional knockout mice (-CAT-cKO mice) were aerosol infected with () H37R with wild-type mice as controls. Four weeks after infection, the mRNA expression of IFN-, TNF-, and TCF-7 in the lungs of mice was measured. CD4, CD8, -catenin, IFN-, and TNF- in mononuclear cells from the lungs and spleens were measured by flow cytometry, and the pathological changes of lungs were also observed. Patients with PTB were enrolled, with blood samples collected and PBMCs isolated. The expressions of -catenin, IFN-, TNF-, and PD-1 in CD4 and CD8 T cells were measured by flow cytometry. Results showed a decreased frequency of and reduced IFN-/TNF- mRNA expression and secretion by CD4 T cells in the lungs of infected -CAT-cKO mice compared with infected wild-type controls, and only slightly more inflammatory changes were observed in the lungs. -catenin expressions in CD4 and CD8 T cells were significantly decreased in blood cells of patients with severe PTB compared with those in mild PTB. The stimulation of peripheral blood mononuclear cells (PBMCs) with lithium chloride (LiCl), a stimulant of -catenin, resulted in the increase in CD4 T cell frequency, as well as their secretion of IFN- and TNF-. -Catenin demonstrated a moderately positive correlation with PD-1 in CD4 T cells. -Catenin along with PD-1 and IFN- in CD4 T cells had a high correlation with those in CD8 T cells. In conclusion, -catenin may be involved in the regulation of Th1 response and CD4 T cell frequency in TB.
-连环蛋白是经典 Wnt/-连环蛋白通路的关键分子。其在结核分枝杆菌（TB）T 细胞中的作用和表达谱尚不清楚。本研究旨在探讨-连环蛋白在 CD4 T 细胞中的作用及其在肺结核（PTB）患者中的表达特征。在这项研究中，用 （）H37R 对 CD4 T 细胞特异性 -连环蛋白条件敲除（-CAT-cKO）小鼠进行气溶胶感染，并用野生型小鼠作为对照。感染 4 周后，测量小鼠肺部 IFN-、TNF-和 TCF-7 的 mRNA 表达。通过流式细胞术测量肺和脾单核细胞中的 CD4、CD8、-连环蛋白、IFN-和 TNF-，并观察肺部的病理变化。招募 PTB 患者，采集血液样本并分离 PBMC。通过流式细胞术测量 CD4 和 CD8 T 细胞中 -连环蛋白、IFN-、TNF-和 PD-1 的表达。结果显示，与感染野生型对照相比，感染 -CAT-cKO 小鼠肺部 CD4 T 细胞的频率降低，IFN-/TNF- mRNA 表达和分泌减少，且肺部观察到的炎症变化仅略有增加。与轻度 PTB 相比，严重 PTB 患者血细胞中 CD4 和 CD8 T 细胞中的 -连环蛋白表达显著降低。用氯化锂（LiCl）刺激外周血单核细胞（PBMC），可增加 CD4 T 细胞的频率，以及其 IFN-和 TNF-的分泌。-连环蛋白与 CD4 T 细胞中的 PD-1 呈中度正相关。CD4 T 细胞中的 -连环蛋白、PD-1 和 IFN-与 CD8 T 细胞中的 -连环蛋白、PD-1 和 IFN-具有高度相关性。总之，-连环蛋白可能参与调节结核分枝杆菌中的 Th1 反应和 CD4 T 细胞频率。
