Year: 2023
Type: conference-abstract
Abstract: CD8+ T cells provide a critical layer of host protection against all manner of pathogens and malignancies. Chromatin remodeling is a critical component of differentiation and acquisition of cytotoxic functions in activated CD8+ T cells, but the mechanisms by which remodeling is achieved in a site-specific way to promote appropriate effector cell fates are poorly understood. Here we identified a role for the ARID1A-containing canonical BAF (cBAF) complex in regulating chromatin accessibility and differentiation of antiviral effector CD8+ T cells. Arid1a was required for CD8+ T cell differentiation into terminal effector and tissue-resident memory cells, but was not required for the formation of long-lived circulating memory cells. Mechanistically, cBAF acted to promote chromatin accessibility at thousands of loci bound by important effector-associated TFs including BHLHE40, T-bet, and BATF. Understanding how chromatin remodeling is regulated in differentiating effector CD8+ T cells will yield insight into optimizing vaccines and adoptive cell therapies for cancer. Supported by grants from NIH (F99 CA274688, R37 AI066232, R01 AI151123)
Source: The Journal of Immunology
Institution: Salk Institute for Biological Studies
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4385686352