CD8⁺ T cells provide host protection against pathogens by differentiating into distinct effector and memory cell subsets, but how chromatin is site-specifically remodeled during their differentiation is unclear. Due to its critical role in regulating chromatin and enhancer accessibility through its nucleosome remodeling activities, we investigated the role of the canonical BAF (cBAF) chromatin remodeling complex in antiviral CD8⁺ T cells during infection. ARID1A, a subunit of cBAF, was recruited early after activation and established de novo open chromatin regions (OCRs) at enhancers. Arid1a deficiency impaired the opening of thousands of activation-induced enhancers, leading to loss of TF binding, dysregulated proliferation and gene expression, and failure to undergo terminal effector differentiation. Although Arid1a was dispensable for circulating memory cell formation, tissue-resident memory (Trm) formation was strongly impaired. Thus, cBAF governs the enhancer landscape of activated CD8⁺ T cells that orchestrates TF recruitment and activity and the acquisition of specific effector and memory differentiation states.

CD8 ⁺ T 细胞通过分化为不同的效应细胞和记忆细胞亚群来提供宿主保护，防止病原体，但染色质在分化过程中如何位点特异性重塑尚不清楚。由于其通过核小体重塑活性在调节染色质和增强子可及性中的关键作用，我们研究了感染期间经典 BAF （cBAF） 染色质重塑复合物在抗病毒 CD8 ⁺ T 细胞中的作用。ARID1A 是 cBAF 的一个亚基，在激活后早期被募集，并在增强子处建立了从头开放染色质区域 （OCR）。Arid1a 缺陷损害了数千个激活诱导的增强子的开放，导致 TF 结合丢失、增殖和基因表达失调，以及无法进行末端效应子分化。尽管 Arid1a 对于循环记忆细胞的形成是必不可少的，但组织驻留记忆 （Trm） 的形成受到严重损害。因此，cBAF 控制活化的 CD8 ⁺ T 细胞的增强子景观，该增强子景观协调 TF 募集和活性以及特定效应子和记忆分化状态的获得。