Canonical BAF Complex activity licenses CD8+ T cell effector fates

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)