Cell death in small intestine mucosa in active celiac disease.

Celiac disease (CD) is an immune-mediated enteropathy that develops in genetically susceptible individuals following gluten ingestion. Lost of epithelia, crypt hyperproliferation and lymphocytic infiltration are characteristics findings in active CD. The major histological change, villus atrophy, is considered a consequence of increased enterocyte apoptosis. Mechanisms including FAS/FASL and MICA/NKG2D interactions, between enterocytes and cytotoxic cells, have been reported in the CD lesion. Though different pathways of cell death have been described, there is no detailed description of the role of these mechanisms in small intestine. Here, we have studied the cellular stress and signaling pathways associated with apoptosis, necroptosis and inflammation in active CD.

Studies by quantitative PCR, confocal microscopy, westernblot and flow cytometry were performed in duodenal biopsies from CD patients and control subjects. We observed higher proliferative response in the crypts, and increased cellular stress but not TUNEL+ cells in differentiated epithelium. In addition, caspase 3 and PARP1 showed higher levels in active CD mucosa accompanied by increased caspase 1. RIPK3, a marker of necroptosis, was found in cells in the crypts in untreated CD.

Our results suggest that different cell death pathways, not only apoptosis, might operate in the small intestine mucosa in untreated CD and can be also linked to pathways of chronic inflammation.