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

Autor: Huihui Chen, Zhiwen Liu, Jie Zha, Li Zeng, Runyan Tang, Chengyuan Tang, Juan Cai, Chongqing Tan, Hong Liu, Zheng Dong, Guochun Chen
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Clinical & Translational Immunology, Vol 12, Iss 8, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2050-0068
DOI: 10.1002/cti2.1464
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje