Paneth Cell Physiology and Pathophysiology in Inflammatory Bowel Disease

Abstract

Paneth cells, named after Joseph Paneth, are distinctive, mucosal cells responsible for secreting the antimicrobial alpha-defensin peptides as well as enzymes including lysozyme and phospholipase A2 that keep the intestinal crypts sterile. Physiologically, they play a key role in defensive mechanisms against intestinal luminal microbes and in the regulation of host innate immunity. Paneth cells derive from fast-cycling crypt base columnar cells, which are associated in crypt regeneration; they differentiate while migrating toward the crypt base, from which they are eventually cleared by phagocytosis. Paneth cells are mostly located within the ileum; in adults they occur normally in sporadic numbers in the caecum to transverse colon but have been reported more distally only in pathological conditions. Paneth cells found in the descending colon, sigmoid, and rectum are “metaplastic” because they are ectopically in an abnormal location. In pathological states, an increase in Paneth cells – known as Paneth cell hyperplasia – may occur in the proximal colon. Paneth cell metaplasia (PCM) has been most often described in inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn’s disease (CD). In adults, it is thought to be a sign of a long-standing colitis history: it correlates with disease duration, and it has been attributed to the effects of repair and regeneration. Guidelines for reporting gastrointestinal biopsies concurred that PCM was an indicator of chronic mucosal cell damage, though it was not included in the data set for IBD reporting as its diagnostic value was then undefined. Paneth cell metaplasia may as well be present in other pathological states. In neonates, PCs are increased in the regenerating bowel following necrotizing enterocolitis but are not seen in self-limiting infectious colitis. In this e-book chapter, we describe the distribution of Paneth cells in symptomatic patients with or without significant gastrointestinal pathology, compare the findings with newly diagnosed IBD, and evaluate the relation between PCM and histological features of chronic disease.