Unsolved mysteries of intestinal M cells

M cells are highly specialised cells present within the epithelium overlying organised lymphoid follicles of the small and large intestine. They play a central role in the initiation of mucosal immune responses by transporting antigens and microorganisms to the underlying lymphoid tissue. In this way the mucosal immune system encounters the limitless variety of antigens that enter the body through the gut mucosa and reacts by mounting specific mucosal and systemic immune responses. Despite the role of M cells in mucosal defence many basic aspects of their biology, the most controversial being their origin within the follicle associated epithelium (FAE), still remain the subjects of debate. Recently, new information on the complex interactions of luminal microorganisms, mucosal immune system, and epithelial cells, that are instrumental in the induction of this cell phenotype, have become available. Here, the most novel data and hypotheses on M cell genesis and function in the gut are reviewed and discussed.