PMC

Proposed model for the pathogenesis of ileal Crohn’s disease and ulcerative colitis. A: In the healthy ileal and colonic mucosa, luminal microbes are sufficiently controlled by an adequate secretion of antimicrobials peptides and a sufficient mucus layer; B: In ileal Crohn’s disease, defective Paneth cell differentiation mediated by a reduction of the Wnt transcription factor TCF4 leads to a decreased Paneth cell defensin secretion, especially in case of NOD2 mutations. This allows the luminal microbes to attach and invade in the mucosa causing inflammation; C: In ulcerative colitis, a defective goblet cell differentiation based on a missing induction of the transcription factors Hath1 and KLF4 results in mucus deficiency enabling the luminal microbes to invade the mucosa and trigger inflammation.