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The differentiation and functional responses of macrophages are shaped by developmental origin, tissue environment, and local inflammatory cues. These signals converge on transcriptional and chromatin-based regulatory mechanisms that establish macrophage identity and enable rapid adaptation to changing local contexts. Lineage-determining transcription factors drive cellular identity by laying out a cell-specific enhancer landscape, whereas signal-dependent transcription factors control local specialization and responses to microbial products and cytokines. Chromatin organization is critical in establishing the plasticity and memory that macrophages show. Chromatin-modifying enzymes are essential regulators of the dynamic programs that control macrophages by erasing, writing, and reading epigenetic marks underlying the cellular programs. In this Review, we highlight recent advances in our understanding of the transcriptional and chromatin dynamics governing macrophage differentiation, specialization, and activation and discuss their roles in health and disease.
Hoeksema et al. (Fri,) studied this question.