2025-03-19 シカゴ大学
<関連情報>
- https://news.uchicago.edu/story/researchers-uncover-surprising-new-way-immune-system-remembers
- https://www.cell.com/cell-systems/fulltext/S2405-4712(25)00004-3
マクロファージの記憶は、転写因子とクロマチンダイナミクスの協調から生まれる Macrophage memory emerges from coordinated transcription factor and chromatin dynamics
Andrew G. Wang∙ Minjun Son∙ Aleksandr Gorin∙ … ∙ Adam Schauer∙ Alexander Hoffmann∙ Savaş Tay
Cell Systems Published:February 11, 2025
DOI:https://doi.org/10.1016/j.cels.2025.101171
Graphical abstract
Highlights
- Macrophages encode memory in NF-κB activation and chromatin accessibility dynamics
- Information on prior stimuli is encoded in individual macrophages
- In vivo systemic inflammation reshapes NF-κB activation dynamics in adult macrophages
- Deep learning on NF-κB and chromatin features predicts memory-conditioned transcription
Summary
Cells of the immune system operate in dynamic microenvironments where the timing, concentration, and order of signaling molecules constantly change. Despite this complexity, immune cells manage to communicate accurately and control inflammation and infection. It is unclear how these dynamic signals are encoded and decoded and if individual cells retain the memory of past exposure to inflammatory molecules. Here, we use live-cell analysis, ATAC sequencing, and an in vivo model of sepsis to show that sequential inflammatory signals induce memory in individual macrophages through reprogramming the nuclear factor κB (NF-κB) network and the chromatin accessibility landscape. We use transcriptomic profiling and deep learning to show that transcription factor and chromatin dynamics coordinate fine-tuned macrophage responses to new inflammatory signals. This work demonstrates how macrophages retain the memory of previous signals despite single-cell variability and elucidates the mechanisms of signal-induced memory in dynamic inflammatory conditions like sepsis.
