Macrophage memory emerges from coordinated transcription factor and chromatin dynamics.

Summary

Using live-cell imaging, ATAC-seq, and an in vivo sepsis model, the authors show that sequential inflammatory stimuli imprint memory in individual macrophages by reprogramming NF-κB signaling and chromatin accessibility. Deep learning and transcriptomics reveal coordinated transcription factor–chromatin dynamics that fine-tune responses to subsequent signals.

Key Findings

• Sequential inflammatory signals induce macrophage memory via reprogramming of the NF-κB network and chromatin accessibility.
• Live-cell analysis, ATAC-seq, and an in vivo sepsis model demonstrate memory encoding at single-cell resolution.
• Transcriptomics and deep learning reveal coordinated transcription factor–chromatin dynamics that fine-tune responses to new stimuli.

Clinical Implications

Identifying NF-κB and chromatin states that encode inflammatory history could guide timing and selection of anti-inflammatory or epigenetic therapies in sepsis and help stratify patients by immune trajectory.

Limitations

• Preclinical mechanistic study without human interventional validation
• Specificity of memory mechanisms across tissue macrophage subsets and pathogens not fully defined

Future Directions

Translate TF–chromatin memory signatures into clinical biomarkers for sepsis endotyping and test timed immunomodulatory or epigenetic interventions.