Early programming of CD8 + T cell response by the orphan nuclear receptor NR4A3

Significance The CD8+ T cell response is crucial in protecting the organism against infections and cancer. This protective response relies on the production of effector molecules and the generation of long-lived memory cells. Understanding the processes governing CD8+ T cell responses is essential for the development of better vaccine strategies and immune cell therapies. Here, we show that deletion of the transcription factor NR4A3 leads to increased memory generation and effector functions. This results from an early impact on the CD8+ T cell transcriptional memory program and on chromatin accessibility for bZIP transcription factors. Thus, we identify NR4A3 as a key regulator of CD8+ T cell function and differentiation, which could have therapeutic implications.