Chen Huihui, Liu Zhiwen, Zha Jie, Zeng Li, Tang Runyan, Tang Chengyuan, Cai Juan, Tan Chongqing, Liu Hong, Dong Zheng, Chen Guochun
Department of Ophthalmology the Second Xiangya Hospital of Central South University Changsha China.
Clinical Immunology Research Center of Central South University Changsha China.
Clin Transl Immunology. 2023 Aug 29;12(8):e1464. doi: 10.1002/cti2.1464. eCollection 2023.
Conventional glucocorticoid (GC) treatment poses significant risks for opportunistic infections due to its suppressive impact on CD4 T cells. This study aimed to explore the mechanisms by which GCs modulate the functionality of CD4 T cells during infection.
We consistently measured FOXP3, inflammatory cytokines and phospho-S6 ribosomal protein levels in CD4 T cells from patients undergoing conventional GC treatment. Using Foxp3 animals, we investigated the dynamic activation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and its correlation with the immunoregulatory function of CD4 T cells under the influence of GCs.
GCs dynamically altered the expression pattern of FOXP3 in CD4 T cells, promoting their acquisition of an active T regulatory (Treg) cell phenotype upon stimulation. Mechanistically, GCs undermined the kinetics of the mTORC1 pathway, which was closely correlated with phenotype conversion and functional properties of CD4 T cells. Dynamic activation of the mTORC1 signaling modified the GC-dampened immunoregulatory capacity of CD4 T cells by phenotypically and functionally bolstering the FOXP3 Treg cells. Interventions targeting the mTORC1 pathway effectively modulated the GC-dampened immunoregulatory capacity of CD4 T cells.
These findings highlight a novel mTORC1-mediated mechanism underlying CD4 T cell immunity in the context of conventional GC treatment.
传统糖皮质激素（GC）治疗因其对CD4⁺T细胞的抑制作用而对机会性感染构成重大风险。本研究旨在探讨GC在感染期间调节CD4⁺T细胞功能的机制。
我们持续检测接受传统GC治疗患者的CD4⁺T细胞中FOXP3、炎性细胞因子和磷酸化S6核糖体蛋白水平。利用Foxp3动物，我们研究了在GC影响下雷帕霉素复合物1（mTORC1）途径的动态激活及其与CD4⁺T细胞免疫调节功能的相关性。
GC动态改变CD4⁺T细胞中FOXP3的表达模式，促使其在受到刺激后获得活化的调节性T（Treg）细胞表型。从机制上讲，GC破坏了mTORC1途径的动力学，这与CD4⁺T细胞的表型转换和功能特性密切相关。mTORC1信号的动态激活通过在表型和功能上增强FOXP3⁺Treg细胞来改变GC减弱的CD4⁺T细胞免疫调节能力。针对mTORC1途径的干预有效调节了GC减弱的CD4⁺T细胞免疫调节能力。
这些发现突出了传统GC治疗背景下CD4⁺T细胞免疫的一种新的mTORC1介导机制。
