Expanding the functional repertoire of macrophages as remote healers.

Abstract

The immune response is essential for maintaining host integrity, and phagocytosis is widely considered as one of its most ancient cellular functions. Accordingly, professional phagocytes such as resident tissue macrophages (RTMs) populate virtually all organs and serve as primary sentinels capable of sensing, engulfing, and eliminating invading pathogens. Yet, reflecting their early evolutionary emergence, RTMs have acquired functions that extend far beyond phagocytosis. In this issue, Salm et al. extend the macrophage toolbox, showing that macrophages residing in the peritoneal cavity function as remote healers. Using various mouse models, they demonstrated that activated peritoneal macrophages accelerate distant skin wound healing through fibronectin secretion, thereby shaping tissue repair at sites beyond their anatomical location. These findings invite us to reconsider macrophages not only as phagocytes and mediators of inflammation but also as active regulators capable of shaping extracellular architecture at a distance.