JunB is required for cytotoxic CD8 T cell response to acute infection

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 to express 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 T cell receptor signal strength. JunB deficiency in CD8+ T cells severely impairs the clonal expansion of effector CD8+ T cells in response to acute Listeria monocytogenes infection. Junb-deficient CD8+ T cells fail to control transcription and chromatin accessibility of a specific set of genes targeted by BATF and IRF4, resulting in impaired cell survival, glycolysis, and cytotoxic CD8+ T cell differentiation. Furthermore, JunB deficiency enhances expression of coinhibitory receptors, including program death receptor 1 (PD1) and T-cell immunoglobulin mucin-3 (Tim3) upon activation of naïve CD8+ T cells. These results indicate that JunB, in collaboration with BATF and IRF4, promotes multiple early events required for generation of cytotoxic CD8+ T cell responses.