Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease

The MICA/B genes (<i>MHC class I chain related genes A and B</i>) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral...

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Detalles Bibliográficos
Autores principales: Allegretti, Yessica Lorena, Bondar, Constanza María, Guzman, Luciana, Cueto Rua, Eduardo, Chopita, Néstor Alfredo, Fuertes, Mercedes, Zwirner, Norberto W., Chirdo, Fernando Gabriel
Formato: Articulo
Lenguaje:Inglés
Publicado: 2013
Materias:
Ciencias Exactas
Ciencias Médicas
Celiac Disease
Cellular Stress
MICA/B genes
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85478
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
Descripción
Sumario:The MICA/B genes (<i>MHC class I chain related genes A and B</i>) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B<SUP>+</SUP> T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B<SUP>+</SUP> B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in <i>in vitro</i> models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role.

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