Neutrophils, known for fighting infections and sometimes damaging tissues in the process, also exist in healthy tissues to help maintain their integrity. Researchers at Yale School of Medicine have uncovered a surprising new role for these immune cells, essential for building and maintaining healthy skin.
In a study with mice, researchers found that neutrophils, in addition to residing in healthy, uninfected skin, also release the “extracellular matrix”—a network of proteins and molecules providing structural support outside cells.
Neutrophils help strengthen and maintain the skin’s structure by depositing proteins like collagen and fibronectin. Previously, this role was thought to be solely the responsibility of fibroblasts, the primary cells in connective tissue.
Neutrophils follow a circadian rhythm in our bodies. Their numbers are low during rest periods but increase during waking hours as they circulate through various tissues. Researchers discovered that these circadian patterns influence mouse skin, with skin stiffness nearly doubling from night to day.
Without the matrix produced by neutrophils, skin tissue loses its stiffness, becomes less firm, and becomes more permeable, compromising its structural integrity and protective function.
Scientists suggest that circadian skin stiffness may offer an evolutionary advantage, as tougher skin during waking and active hours could be beneficial. Although these findings were observed in mice, researchers believe the same pattern likely occurs in humans, given that human neutrophils also follow a circadian rhythm. Evidence of neutrophils producing extracellular matrix in human tissue samples further supports the idea that these results are relevant across species.
Scientists have also found that the production of extracellular matrix proteins causes neutrophils to contribute to wound protection. This creates a barrier that blocks microbes and toxins from entering. This function is critical, especially for immunocompromised individuals with low neutrophil levels, as their weakened barriers can lead to increased vulnerability to infections.
The study hints at using neutrophils’ versatile roles in new therapies, but it mainly emphasizes the need to rethink how we understand immune cells.
Journal Reference
- Vicanolo, T., Özcan, A., Li, J.L. et al. Matrix-producing neutrophils populate and shield the skin. Nature (2025). DOI: 10.1038/s41586-025-08741-5