Here, by differentiating human inducible pluripotent stem cells (iPSCs) or murine adult IESCs and utilizing compound mutant mice (Gilbert et al, 2012a, 2015), we defined a population of IESCs by which constitutive STAT5 activation (Ca-pYSTAT5) regenerated the niche, and unveiled the effects of defective JAK2-STAT5 signaling upon IESC niche cells, leading to susceptibility to enteric infection and ileocolitis. This evidence concerns the gene STAT5B and ileocolitis.