JunB is required for CD8+ T cell responses to acute infections

Abstract

Basic-leucine zipper transcription factor ATF-like (BATF) and interferon regulatory factor 4 (IRF4) are crucial transcription factors for the generation of cytotoxic effector and memory CD8+ T cells. JunB is required for expression of genes controlled by BATF and IRF4 in CD4+ T cell responses, but the role of JunB in CD8+ T cells remains unknown. Here, we demonstrate that JunB is essential for cytotoxic CD8+ T cell responses. JunB expression is transiently induced, depending on the T cell receptor signal strength. JunB deficiency severely impairs the clonal expansion of effector CD8+ T cells in response to acute infection with Listeria monocytogenes. Junb-deficient CD8+ T cells fail to control transcription and chromatin accessibility of a specific set of genes regulated by BATF and IRF4, resulting in impaired cell survival, glycolysis, and cytotoxic CD8+ T cell differentiation. Furthermore, JunB deficiency enhances the expression of co-inhibitory receptors, including programmed cell death 1 (PD-1) and T cell immunoglobulin mucin-3 (TIM3) upon activation of naive CD8+ T cells. These results indicate that JunB, in collaboration with BATF and IRF4, promotes multiple key events in the early stage of cytotoxic CD8+ T cell responses.

Keywords: AP-1; apoptosis; co-inhibitory molecules; effector and memory CD8+ T cells; glycolysis.