Year: 2025
Type: article
Abstract: Description Increasing emphasis on considering sex as a biological variable has revealed underappreciated sex differences in immune responses. As a critical driver of sexual dimorphism, our group and others have described a role for the androgen receptor (AR) in limiting CD8 T cell anti-tumor activity by inhibiting IFNγ production and responses to immune checkpoint blockade. However, the mechanisms by which AR regulates CD8 T cell differentiation and function, and whether AR impacts CD8 T cell responses to acute infection are unknown. To define the AR regulatory network in T cells, we overexpressed AR in human T cells and revealed AR-mediated epigenetic and transcriptional regulation of effector- and memory-associated genes and AR protein interactions with epigenetic regulators such as the BAF complex and histone deacetylases. In mouse models of infection, we show that genetic deletion of Ar in CD8 T cells using a lineage-specific cre-lox system enhances the effector response by increasing cytokine production, proliferation, and effector differentiation. Furthermore, deletion of Ar in CD8 T cells skews memory differentiation and improves memory protection. Interestingly, AR expression rapidly increases in CD8 T cells during priming, which is associated with AR-induced changes in chromatin accessibility. These data suggest that AR regulates epigenetic and transcriptional changes induced during T cell activation and differentiation, thereby tuning CD8 T cell effector and memory responses. Funding Sources Supported by NCI R37CA263592-01; 5T32CA254888-03 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)
Source: The Journal of Immunology
Authors: Reed M. Hawkins, Fanny Polesso, Aaron Ko, Rachel Huynh, John Cheney, Amy Moran
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416448656
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