Ontology highlight
ABSTRACT: Objectives
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.Methods
We consistently measured FOXP3, inflammatory cytokines and phospho-S6 ribosomal protein levels in CD4+ T cells from patients undergoing conventional GC treatment. Using Foxp3EGFP 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.Results
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.Conclusion
These findings highlight a novel mTORC1-mediated mechanism underlying CD4+ T cell immunity in the context of conventional GC treatment.
SUBMITTER: Chen H
PROVIDER: S-EPMC10463561 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Chen Huihui H Liu Zhiwen Z Zha Jie J Zeng Li L Tang Runyan R Tang Chengyuan C Cai Juan J Tan Chongqing C Liu Hong H Dong Zheng Z Chen Guochun G
Clinical & translational immunology 20230829 8
<h4>Objectives</h4>Conventional glucocorticoid (GC) treatment poses significant risks for opportunistic infections due to its suppressive impact on CD4<sup>+</sup> T cells. This study aimed to explore the mechanisms by which GCs modulate the functionality of CD4<sup>+</sup> T cells during infection.<h4>Methods</h4>We consistently measured FOXP3, inflammatory cytokines and phospho-S6 ribosomal protein levels in CD4<sup>+</sup> T cells from patients undergoing conventional GC treatment. Using Foxp ...[more]