TGF-β: A master regulator of tissue-resident macrophage identity and function #immunology
Tissue-resident macrophages exhibit remarkable plasticity, dynamically adapting to their local environment and adopting tissue-specific phenotypes that support organ homeostasis. The underlying identity-determining transcriptional programs are instructed by microenvironmental cues. Transforming growth factor-β (TGF-β), which has long been recognized for its role in immunosuppression, has recently emerged as a pivotal determinant of tissue macrophage identity. In this review, we highlight how TGF-β shapes innate immunity by driving macrophage imprinting and transcriptional programming within defined tissue niches. We emphasize that the spatial and temporal regulation of TGF-β activation—rather than its overall abundance—governs its divergent effects on immune cells. Understanding the precise mechanisms promises to spur the development of more selective therapeutic strategies for modulating macrophage function in health and disease.
