Gene regulatory basis of bystander activation in CD8+ T cells (ATAC-seq)

The immune system is stratified into layers of specialized cells with distinct functions. Recently, Lin28b was shown to serve as a master regulator of fetal lymphopoiesis and program the development of more innate-like lymphocytes in early life. However, it is still unclear how Lin28b alters the function of fetal-derived lymphocytes and protects the host against infection. In this report, we examined how Lin28b transcriptionally and epigenetically programs murine CD8+ T cells for innate immune defense and translated our key findings to human CD8+ T cells. We found that Lin28b operates as a gatekeeper, opening the door to a hidden diversity of phenotypes that are unveiled upon stimulation with innate cytokines. In particular, Lin28b promotes a transcriptionally and functionally diverse pool of cells through chromatin remodeling. As a result, neonatal CD8+ T cells are able to deploy a bet-hedging immune strategy and protect the host against a wide range of unrelated pathogens. Profiling chromatin landscape of gBT-I TCR tg adult, neonatal and Lin28b Tg adult CD8+ T cells treated with IL-2 or IL-12/18 by high-throughput sequencing, in 2, 3 or 6 replicates, using Illumina NextSeq500.