More recently, through loss-of-function and rescue-phenotype studies, RANKL is shown to be a receptor activator of NF-κB ligand and play a role in differentiation of M cells.
RANKL is expressed throughout the small intestine, facilitates uptake of pathogens such as Salmonella, and is the most critical factor M cell differentiation.
For example, the type III secretion system effector protein SopB activates the transition of M cells from enterocytes.
[1] In one case, the SopB effector protein mentioned above is secreted to trigger fast differentiation of enterocytes localized in the FAE by initiation of epithelial to mesenchymal transition in these cells.
[8] M cells do not secrete mucus or digestive enzymes, and have a thinner glycocalyx, which allows them to have easy access to the intestinal lumen for endocytosis of antigens.
The main function of M cells is the selective endocytosis of antigens, and transporting them to intraepithelial macrophages and lymphocytes, which then migrate to lymph nodes where an immune response can be initiated.
In females that are not lactating, when M cells recognize antigen in the gut, they stimulate production of many Immunoglobulin A (IgA) antibodies.
Thus, the mammary gland and breast milk have critical roles alongside M cells in mucosal immune system.
[10] M cells are exploited by several pathogenic gram-negative bacteria including Shigella flexneri, Salmonella typhimurium, and Yersinia pseudotuberculosis, as well as infectious prions, such as in bovine spongiform encephalitis (Mad-cow disease), as a way of penetrating the intestinal epithelium.