Microbiota-immune cell interactions play a vital role in host defense against potentially harmful external organisms, such as viruses and bacteria, and environmental agents including food. Microfold(M) cells are specialized epithelial cells found in the gut epithelium that are pivotally positioned to sample gut contents and importantly actively transport antigens across the gut epithelium. Critically, they link the gut lumen with the immune cell network positioning them to instruct appropriate immune responses, including the production of immunoglobin A against invading pathogens. Exactly how they orchestrate these events, however, is not clear.
Despite their critical function, to date few specific tools exist to study intestinal M cells, the molecular mechanisms that regulate their generation or how they drive mucosal immunity. To overcome this gap, we have generated novel reporter mouse strains to identify M cells allowing us to show that SpiB expressing M cells are present along the entire intestinal tract and not only localized to Peyer’s Patch as previously thought. Analysis of gut epithelial cells at these different sites in the gut using single cell RNA sequencing revealed tissue-specific heterogeneity allowing us to define distinct gene expression signatures for M cells based on their location. These molecular blueprints identify novel maturation programs that are likely to be dependent on local environmental cues shaped by the microbiota and that influence induction of immune responses. Furthermore, we propose that the functional pathways of localized M cells significantly impact gut region-specific disease and plan to explore these pathways and their impact on gut integrity during homeostasis and infection.