Deoxycorticosterone Reshapes CD8+ T Cell State and Effector Function Through Distinct Metabolic Signaling Programs
Year: 2026
Type: article
Abstract: Background/Objectives: Whether individual endogenous corticosteroids exert distinct immunoregulatory effects on CD8+ T cells remains poorly understood. We investigated how deoxycorticosterone (DOC) affects CD8+ T cell state and function. Methods: Primary mouse CD8+ T cells were activated with anti-CD3/CD28 and IL-2 in the presence or absence of DOC. Flow cytometry was used to assess exhaustion-associated markers and effector function, and pharmacological perturbations were used to examine the involvement of AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and protein kinase B (AKT) signaling. Results: DOC promoted an exhaustion-associated phenotype characterized by increased frequencies of PD-1+LAG-3+ and PD-1+TIM-3+ cells and elevated TOX expression. DOC concurrently impaired effector function, reducing IFN-γ/TNF co-production, granzyme B expression, and IL-2 production. Pharmacological inhibition of AMPK or activation of mTOR partially attenuated exhaustion-associated features induced by DOC, whereas AKT activation partially restored effector function. Conclusions: DOC directly reshapes CD8+ T cell state and function in vitro, with exhaustion-associated and effector responses exhibiting distinct pharmacological signaling dependencies. These findings identify DOC as a previously underappreciated endogenous corticosteroid capable of modulating CD8+ T cell biology.
Source: Biomedicines
Authors: Tao Li, Anqi Chen, Siqi Zhou, Gang Xue
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,137
Awards: G9001302364, G9001303829
OpenAlex ID: W7222358703