Changes in mucosal MICA expression as part of the early events involved in the immunopathogenesis of coeliac disease

ALLEGRETTI Y; RULLI E; ZAIDMAN V; GUZMAN L; CUETO RUA E; DRUT E; ZWIRNER N; CHIRDO F

Amsterdam

Congreso; 13th International Coeliac Disease Symposium; 2009

International Coeliac Disease Symposium

MICA is a non classical MHC class I polymorphic protein modulated by cellular distress. Mucosal MICA levels were reported to correlate with gluten ingestion and IL-15 mediated its induction. We evaluated MICA expression and its modulation in paediatric small intestinal mucosa. Immunohistochemistry studies on whole biopsy samples showed increased MICA staining in untreated coeliac patients compared to controls; this difference was not observed in 2 out of 9 atrophic samples. RT-qPCR showed higher MICA expression in active CD, but not significant differences were found, p=0,33. Short term incubation with rIL-15 or a-gliadin p31-43 in both groups did not induce MICA expression. Confocal microscopy showed that MICA was commonly present in the perinuclear region of the enterocytes; its expression was very low in normal intestine, but it was upregulated in mild and severe enteropathy. In addition to enterocytes, MICA was expressed in other mucosal cells, such as CD138+ (mostly plasma cells) and CD7+ cells. The percentages of MICA+ cells studied were similar in severe enteropathy and control samples, however, absolute numbers were increased in enteropathy. MICA staining was much more intense in CD7+ and CD138+ cells than in enterocytes. Other MICA+ cells remain to be identified. Caco-2 cells were incubated with IL-15 (50ng/ml, 24hs) or subjected to different stress stimuli. qPCR studies showed that IL-15 treatment did not induce MICA expression. Oxidative stress (AsONa) upregulated MICA mRNA levels, meanwhile the UPR inductor Thapsigargin, and high temperature (39,5◦C) did not. All stress stimuli rearranged normal cytoplasmic MICA distribution into granules. In conclusion, MICA is expressed not only in enterocytes but also in other cells in intestinal mucosa. We failed to show an IL-15 induction of MICA expression on whole biopsies and Caco-2 cells. These data suggest that the higher MICA levels in atrophic mucosa are largely due to an increased cellularity.