Paneth cell

**Location and histology** - Found at the base of the crypts of Lieberkühn in the small intestine, most numerous in the ileum. They are also found in the cecum and ascending colon, but only in metaplasia elsewhere in the colon. - They are pyramidal cells with prominent apical eosinophilic (bright pink) secretory granules on H&E and a basal nucleus. The abundant rough ER makes the basal cytoplasm basophilic. - They are long-lived, with a lifespan of about 20 days. This is much longer than the ~3-5 days of other intestinal epithelial cells, which migrate up the villus.

**Function** - Innate mucosal immunity: they secrete lysozyme (breaks down bacterial peptidoglycan), α-defensins (HD5 and HD6 in humans; cryptdins in mice), phospholipase A2, and TNF-α. Secretion is stimulated by bacterial products and cholinergic input. - They regulate the gut microbiota and protect against enteric pathogens. - Niche support: they supply Wnt3, EGF, and Notch ligands to adjacent Lgr5+ intestinal stem cells at the crypt base. This maintains stem cell function and epithelial renewal. - Defensins form pores in microbial membranes.

**Embryology and differentiation** - They arise from crypt stem cells (Lgr5+) and, unlike other epithelial cells, migrate downward to the crypt base. - Differentiation depends on Wnt signaling (Tcf4/Tcf7l2, Sox9).

**Clinical correlations** - **Crohn disease:** NOD2 (CARD15) loss-of-function mutations impair Paneth cell function and defensin production, which contributes to dysbiosis and ileal inflammation. Autophagy gene variants (ATG16L1) also cause Paneth cell granule abnormalities. - **Necrotizing enterocolitis (NEC):** Paneth cell dysfunction or immaturity in premature infants may contribute. - **Metaplasia:** Paneth cell metaplasia in the distal colon indicates chronic injury, such as long-standing ulcerative colitis or Crohn disease. - **Other:** Paneth cells are reduced in graft-versus-host disease of the gut. Tumors with Paneth cell differentiation, such as some colorectal adenocarcinomas, are rare.

**High-yield comparison of small intestinal epithelial cells** - **Enterocytes:** absorptive, with a brush border. - **Goblet cells:** mucus-secreting (mucin). - **Enteroendocrine cells:** secrete CCK, secretin, GIP, and others. - **M cells:** overlie Peyer patches and sample antigen. - **Paneth cells:** antimicrobial defense and stem cell niche. - **Tuft cells:** chemosensory, with a role in the type 2 immune response to helminths.

**Board pearl:** "Bright pink granules at the crypt base = Paneth cell → lysozyme and defensins." The Crohn disease association is NOD2 → defective Paneth cell function.