Researchers from the Clevers Group have published new findings in Nature about the function of microfold cells (M cells) in the human small intestine. Previously, most understanding of M cells came from studies conducted on mice, leaving questions about whether human M cells had similar or different roles.
The research team used lab-grown human intestinal organoids to study these cells. By modifying culture conditions, they were able to enrich for M cells and then confirm their characteristics using high-resolution electron microscopy at Maastricht University. This approach allowed them to compare human M cell function directly with that of mouse M cells.
One key discovery was that ICAM2 serves as a specific marker for identifying developing M cells. Using ICAM2 alongside established markers SPIB and GP2, researchers tracked the progression of organoid M cells through various stages of maturity. They found that factors essential for dendritic cell development also play a role in the maturation of human M cells. Further analysis revealed that human M cells share many genes with dendritic immune cells, including those responsible for antigen presentation.
"The antigen-presenting function of human M cells surprised us," said co-first author Daisong Wang. "This function is typically reserved for professional antigen-presenting immune cells. Mouse M cells cannot do this, so it marks a clear difference between species." Human M cells not only transport bacteria and antigens like their mouse counterparts but can also process antigens and present them directly to T helper white blood cells.
The study went further by investigating whether these human M cells could present gluten antigens—proteins known to trigger an inflammatory response in celiac disease patients. Supported by Chugai Pharmaceutical, researchers used a specialized antibody to detect presented gluten antigens and found that human M cells could take up gluten, break it down, and present it to T-cells in co-culture experiments. "Because this process resembles the first steps of celiac disease, these results suggest that M cells may play a central role in the disease," explained co-first author Sangho Lim.
This research builds on previous discoveries related to celiac disease originating from Utrecht, notably observations made during World War II by Dutch pediatrician W.K. Dicke regarding children’s responses to wheat scarcity and reintroduction.
According to the authors, understanding this newly discovered function may provide insight into immune system imbalances such as food sensitivities and inflammatory bowel diseases. The team’s ability to model gluten-specific responses could aid future studies focused on celiac disease mechanisms.
Looking ahead, researchers aim to investigate how these findings translate within real intestinal tissue environments and hope their work will inspire new approaches in diagnostics or treatment strategies for gut-related disorders. "By revealing new features of human M cells, we offer a framework for deeper studies of gut immunity," Daisong Wang said. "Our datasets are open to all researchers."
