Identification of microfold cell-inducer (MCi) cells that regulate IgA production and diversify the gut microbiota

Mammalian intestine hosts trillions of microbes and deploys a large number of immune cells. A continuous dialogue between immune cells and luminal microbes is critical for the maintenance of intestinal homeostasis. Intestinal epithelium is a single-layered cell sheet that separates microbes and the intestinal immune system. The appropriate development and maintenance of epithelium is essential for the clearance of pathogens and the prevention of excess immune reactions against commensal bacteria. Microfold (M) cell is one type of the epithelial cells specialized for bacterial sampling from the lumen and initiate germinal center formation and IgA production in the gut associated lymphoid tissues (GALTs) including Peyer’s patches (PPs). Previous reports showed that TNF family cytokine RANKL is indispensable for M cell development. However, the precise producer of RANKL has not been determined.
In this talk, I show that previously unrecognized subepithelial mesenchymal cells express RANKL and serve as M cell-inducer (MCi) cells. The specific deletion of RANKL in mesenchymal cells caused impaired M cell differentiation as well as reduced IgA production against gut microbes, resulting in an altered gut microbial composition and a decrease in microbial diversity. Thus, MCi cells play a fundamental role in the maintenance of intestinal immune homeostasis.