Peyer's patch lymphocytes cocultured with Caco-2 cells trigger the phenotypic conversion of enterocytes into cells that express morphological and functional M-cell properties. We report a technical update for setting up this model, which will enable the study of M-cell biology, the identification by biochemical approaches of molecules involved in the interaction of microorganisms with M cells, and the development of vectors that would efficiently target the mucosal immune system.