| First Author | Bevington SL | Year | 2020 |
| Journal | EMBO J | Volume | 39 |
| Issue | 22 | Pages | e105220 |
| PubMed ID | 32930455 | Mgi Jnum | J:330746 |
| Mgi Id | MGI:6714547 | Doi | 10.15252/embj.2020105220 |
| Citation | Bevington SL, et al. (2020) IL-2/IL-7-inducible factors pioneer the path to T cell differentiation in advance of lineage-defining factors. EMBO J 39(22):e105220 |
| abstractText | When dormant naive T cells first become activated by antigen-presenting cells, they express the autocrine growth factor IL-2 which transforms them into rapidly dividing effector T cells. During this process, hundreds of genes undergo epigenetic reprogramming for efficient activation, and also for potential reactivation after they return to quiescence as memory T cells. However, the relative contributions of IL-2 and T cell receptor signaling to this process are unknown. Here, we show that IL-2 signaling is required to maintain open chromatin at hundreds of gene regulatory elements, many of which control subsequent stimulus-dependent alternative pathways of T cell differentiation. We demonstrate that IL-2 activates binding of AP-1 and STAT5 at sites that can subsequently bind lineage-determining transcription factors, depending upon what other external factors exist in the local T cell environment. Once established, priming can also be maintained by the stroma-derived homeostatic cytokine IL-7, and priming diminishes if Il7r is subsequently deleted in vivo. Hence, IL-2 is not just a growth factor; it lays the foundation for T cell differentiation and immunological memory. |
