The macrophage disappearance reaction (MDR) was originally proposed to explain the loss of peritoneal macrophages in inflammation but has since been extended across tissues and diseases. MDR involves multiple processes, including cell death, differentiation, loss of identity, and the formation of aggregates rendering the cells difficult to isolate. This spectrum of modalities, coupled with our increased understanding of how the microenvironment shapes macrophage identities, highlights the need to reassess MDR within the framework of modern macrophage biology. We postulate that rethinking MDR in the context of the tissue niche offers insights into macrophage dynamics and demonstrates that macrophage loss is not a passive outcome of inflammation but rather an active process shaping immune networks, tissue responses, and ultimately organ function.
Liu et al. (Wed,) studied this question.