Abstract

Upon infection, naïve CD8+ T cells differentiate into cytotoxic effector cells to eliminate the pathogen-infected cells. Although many mechanisms underlying this process have been demonstrated, the regulatory role of chromatin remodel system in this process remains largely unknown. Here we showed that BRD7, a component of the polybromo-associated BRG1-associated factor complex (PBAF), was required for naïve CD8+ T cells to differentiate into functional short-lived effector cells (SLECs) in response to acute infections caused by influenza virus or lymphocytic choriomeningitis virus (LCMV). BRD7-deficiency in CD8+ T cells resulted in profound defects in effector population and functions, thereby impairing viral clearance and host recovery. Further mechanical studies indicated that the expression of BRD7 significantly turned to high from naïve CD8+ T cells to effector cells, bridged BRG1 and PBRM1 to the core module of PBAF complex, consequently facilitating the assembly of PBAF complex rather than BAF complex in the effector cells. The PBAF complex changed the chromatin accessibility at the loci of Tbx21 gene and up-regulated its expression, leading to the maturation of effector T cells. Our research confirms BRD7 and the PBAF complex are key in CD8+ T cell development and present a significant target for advancing immune therapies.

Authors

Feng Huang, Yingtong Lin, Yidan Qiao, Yaochang Yuan, Zhihan Zhong, Baohong Luo, Yating Wu, Jun Liu, Jingliang Chen, Wanying Zhang, Hui Zhang, Bingfeng Liu

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