Macrophages: Key Players in Salivary Gland Development
New research from the Icahn School of Medicine at Mount Sinai reveals a surprising role for macrophages – traditionally known as immune cells responsible for clearing debris – in the intricate process of embryonic salivary gland development. Ali May, PhD, an assistant professor at the Icahn School of Medicine, presented these findings on February 19, 2026, challenging conventional understanding of these cells and highlighting their potential to guide organ formation.
Redefining Macrophages: Beyond “Garbage Collectors”
For years, macrophages have been primarily understood as “garbage collectors,” engulfing and digesting dead cells and foreign materials. However, Dr. May’s work suggests a far more dynamic role. She encourages a shift in perspective, viewing macrophages as active participants in development, capable of communicating with epithelial cells, nerves, and surrounding tissues. This re-evaluation stems from her prior research on the intersection of the immune system and the nervous system during neuronal development.
Macrophages and Branching Morphogenesis
Dr. May’s lab investigates how different macrophage populations influence branching morphogenesis – the tree-like growth of ducts and secretory units crucial for glandular organs. Using a genetic system to selectively remove macrophages during critical stages of salivary gland development, the team observed a significant reduction in branching. Normally, developing salivary glands exhibit numerous, smaller buds. However, when macrophages were depleted, the glands displayed fewer, but larger buds, indicating impaired branching.
Impact on Epithelial Cell Maturation
The absence of macrophages not only hindered branching but also impeded the maturation of essential epithelial cells responsible for saliva production, and transport. Gene expression analysis revealed decreased expression of genes associated with secretory acinar cells, ductal cells, and other key epithelial markers. The team observed developmental effects on non-epithelial cell types, with some genes linked to glial and neural cell markers, suggesting a potential role for macrophages in shaping the developing nervous system within the gland.
TNF Signaling: A Key Communication Pathway
Dr. May’s research identified tumor necrosis factor (TNF), a cytokine typically associated with inflammation, as a crucial signaling molecule in macrophage-epithelial communication. While TNF is often linked to injury and disease, the study found its expression in macrophages near the developing epithelial compartment, with a corresponding upregulation of the TNF receptor on epithelial cells. In vitro experiments demonstrated that adding TNF to isolated embryonic salivary gland epithelial cells significantly increased branching and growth, promoting the formation of ducts.
Distinct Macrophage Populations and “Cuddling” Behavior
Dr. May’s team discovered that salivary glands contain two distinct macrophage populations: a long-lived group originating from the yolk sac and a later-arriving, monocyte-derived population. These populations occupy different niches within the developing gland and appear to have different functions. Live imaging revealed a unique behavior where macrophages physically cross the basement membrane to encapsulate epithelial cells – a phenomenon Dr. May playfully termed “cuddling.” This interaction appears to be linked to epithelial cell division, though the exact mechanism (whether macrophages recruit dividing cells or actively trigger proliferation) is still under investigation.
About Dr. Ali May
Ali May, PhD, is an Assistant Professor of Stem Cell Biology and Regenerative Medicine, and Otolaryngology at the Icahn School of Medicine at Mount Sinai. She is also a member of the Black Family Stem Cell Institute and the Institute of Airway Sciences. Her research focuses on the cellular and molecular mechanisms governing organ formation and regeneration, particularly in airway and oral epithelial tissues.
The post Macrophages Guide Salivary Gland Development: New Research Reveals Key Role appeared first on Archynewsy.