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Glucocorticoid regulation of the mTORC1 pathway modulates CD4+ T cell responses during infection.


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

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Publications

Glucocorticoid regulation of the mTORC1 pathway modulates CD4<sup>+</sup> T cell responses during infection.

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]

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