Hidden in hair follicles, immune ‘sentinel’ cells may help skin detect microbes

Researchers at the School of Medicine at the University of California, Riverside have discovered previously unrecognized immune surveillance structures in the skin. Found within hair follicles, the cells resemble M (microfold) cells—specialized epithelial cells traditionally associated with the gut and airway tissues.

The findings, published in Frontiers in Cell and Developmental Biology, suggest that the skin may use specialized “sentinel” cells located within hair follicle structures to monitor environmental exposure and microbial presence, expanding current understanding of how barrier tissues defend the body. The work was done in mice.

Senior author Dr. David Lo, a distinguished professor of biomedical sciences, explained that unlike the gut and airway epithelium, which consists of a single-cell layer allowing relatively direct environmental sampling, the skin is composed of multiple stratified layers that form a more robust physical barrier.

“This raises a long-standing question in immunology: how does the skin efficiently monitor external threats despite its thickness?” Lo said.

Lo’s team proposes that hair follicles may act as localized “gateway” structures that concentrate both environmental material and immune sensing activity. Within these niches, the team identified M cell-like sentinel cells that appear to participate in localized immune responses, particularly to Gram-positive bacteria—bacteria that can cause a range of infections, from food poisoning to serious respiratory diseases.

“Hair follicles may represent a central hub for immune surveillance in the skin,” said Diana Del Castillo, the first author of the paper and a graduate student in Lo’s lab. “These structures bring together environmental exposure, immune sensing, and potentially even neural signaling in a highly localized environment.”

While the research team is still characterizing the cells, early findings suggest they are part of a broader category of epithelial surveillance mechanisms that may exist across multiple tissues.

The discovery also raises new questions about how immune and sensory systems may be integrated. Hair follicles are already known to contribute to touch sensation, and the newly identified structures appear to be in regions closely associated with nerve endings, suggesting a potential link between immune detection and sensory signaling.

Lo said future work will focus on detailed anatomical mapping of these cells, particularly in whisker follicles in animal models since whiskers have dense innervation and complex structure.

“We would like to better understand how these cells interact with surrounding nerve and immune cells, and whether similar systems exist in humans,” he said.

Although the study is still in early stages, the findings may have future implications for understanding skin infections, immune disorders, and the development of topical therapeutics.

“We’re only beginning to understand how these systems are organized,” Lo said. “But they suggest the skin is far more dynamically involved in immune surveillance than previously thought.”

Del Castillo said the study highlights a potential shift in how scientists view barrier tissues—not as passive protective layers, but as active and highly specialized sensory and immune interfaces.

“Our study adds to growing evidence that epithelial barriers across tissues share more diverse and dynamic immune-related functions than previously recognized, particularly in their ability to respond rapidly to microbial stimuli,” she said.

Lo and Del Castillo were joined in the study by Hannah Kim and Sumaya Troy Alaama.

The research was supported by funds from the UCR School of Medicine.

The title of the paper is “Evidence for murine cutaneous immune surveillance localized to hair follicle epithelium.”