MICA expression in normal and coeliac intestinal mucosa

ALLEGRETTI Y; CUETO RUA E; NAMFITO G; HERNANDEZ K; FUERTES M; ZWIRNER N; CHIRDO FG

Cordoba

Congreso; VII Latin American Congress of Immunology; 2005

Asociación Latinoamericana de Inmunología

MIC (MHC class I chain related) A is expressed in intestinal epithelia under normal conditions, but its expression is upregulated after cellular stress. NKG2D receptor, expressed by intraepithelial lymphocytes, activates cellular citotoxicity when interacts with MICA positive cells. It would constitute the main mechanism to eliminate stressed enterocytes. Furthermore, new evidence supports that IL-15-mediated innate response determines the initial inflammatory events in the intestinal mucosa of coeliac patients. The aim of the study was to investigate the expression of MICA in small intestine with normal histology, presenting inflammatory signs or villus atrophy. Patients enrolled in the study were younger than 4 years old. Biopsy samples were collected during the routine coeliac disease diagnostic protocol and grouped, according to the histology, in normal or lesion type I, II or IV, where type IV corresponds to the typical villus atrophy. Sections of small intestinal biopsies were stained for immunohistochemistry analysis using either 15 µg/ml of MIC A-specific monoclonal antibody or an isotype-matched control antibody. Normal intestinal tissue (n= 5) express MICA at low levels. Samples (4/5) from Group I, (5/7) from Group II and (6/8) from Group IV, were positive for MICA staining. Strikingly, in two cases presenting villus atrophy, staining was very low. Staining was intracellular and homogeneous in enterocytes in all cases but intensity was variable. In conclusion, MIC A is induced in damaged intestinal mucosa. These results point out to a role of MICA expression in the initial inflammatory events in the intestinal mucosa.