記憶T細胞の迅速な想起は、エピゲノムと補因子相互作用によって決定される記憶特異的AP-1リクルートメントによって駆動される

CD4 T cell memory is essential for long-lasting protective immunity to repeat infections. Unlike naïve T cells, memory cells possess rapid recall ability to quickly produce effector molecules in response to antigen re-exposure. This ability was shown to be associated with epigenetic gene poising. Here, we examine how the activation-inducible transcription factors, AP□1 and NF□κB, regulate rapid recall gene expression. We found that AP-1 is required for their induction and that the enhanced induction of rapid recall genes in memory cells is associated with memory-specific binding of AP□1. Memory-specific AP□1 binding, in turn, is enabled by enhanced chromatin accessibility and reduced DNA methylation at regulatory elements. As the AP-1 DNA-binding motif itself does not contain methylatable CpGs, methylation likely affects the binding of AP-1 co-factors, such as ETS proteins, or accessibility of the region in general. Finally, both common and memory-specific AP□1/NF□κB binding sites show strong overlap with autoimmune and inflammatory disease risk variants, highlighting the clinical relevance of memory T cell epigenetic regulation.