In about 70% of patients Crohn's disease (CD) affects the small intestine. This 
disease location is stable over time and associated with a genetic background 
different from isolated colonic disease. A characteristic feature of small 
intestinal host defense is the presence of Paneth cells at the bottom of the 
crypts of Lieberkühn. These cells produce different broad spectrum antimicrobial 
peptides (AMPs) most abundantly the α-defensins HD-5 and -6 (DEFA5 und DEFA6). 
In small intestinal Crohn's disease both these PC products are specifically 
reduced. As a functional consequence, ileal extracts from Crohn's disease 
patients are compromised in clearing bacteria and enteroadherent E. coli 
colonize the mucosa. Mechanisms for defective antimicrobial Paneth cell function 
are complex and include an association with a NOD2 loss of function mutation, a 
disturbance of the Wnt pathway transcription factor TCF7L2 (also known as TCF4), 
the autophagy factor ATG16L1, the endosomal stress protein XBP1, the toll-like 
receptor TLR9, the calcium mediated potassium channel KCNN4 as well as mutations 
or inactivation of HD5. Thus we conclude that small intestinal Crohn's disease 
is most likely a complex disease of the Paneth cell: Paneth's disease.