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Abstract:

The MICA/B genes (MHC class I chain related genes A and B) 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+ T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B+ 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 in vitro 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. © 2013 Allegretti et al.

Registro:

Documento: Artículo
Título:Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease
Autor:Allegretti, Y.L.; Bondar, C.; Guzman, L.; Cueto Rua, E.; Chopita, N.; Fuertes, M.; Zwirner, N.W.; Chirdo, F.G.
Filiación:Laboratorio de Investigación en el Sistema Inmune - LISIN, Departamento de Ciencias Biológicas, Universidad Nacional de La Plata, La Plata, Argentina
Servicio de Gastroenterología, Hospital de Niños Sor María Ludovica, La Plata, Argentina
Servicio de Gastroenterología, Hospital San Martin La Plata, La Plata, Argentina
Laboratorio de Fisiopatología de la Inmunidad Innata, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Microbiología, Parasitología e Inmunología, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:CD20 antigen; CD3 antigen; CD68 antigen; CD7 antigen; glycoprotein p 15095; major histocompatibility antigen class 1; major histocompatibility antigen class 2; syndecan 1; article; B lymphocyte; celiac disease; cell stress; cellular distribution; child; clinical article; confocal microscopy; controlled study; disease severity; endoplasmic reticulum stress; flow cytometry; gene; gene expression regulation; human; human cell; human tissue; immune dysregulation; immunofluorescence test; immunopathogenesis; intestine biopsy; lamina propria; macrophage; MICA gene; MICAB gene; oxidative stress; preschool child; protein localization; small intestine mucosa; B-Lymphocytes; Celiac Disease; Child, Preschool; Duodenum; Enterocytes; Female; Gene Expression; Histocompatibility Antigens Class I; Humans; Intestinal Mucosa; Macrophages; Male; Plasma Cells; Severity of Illness Index; Stress, Physiological; T-Lymphocytes
Año:2013
Volumen:8
Número:9
DOI: http://dx.doi.org/10.1371/journal.pone.0073658
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CODEN:POLNC
CAS:syndecan 1, 128559-86-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n9_p_Allegretti

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Citas:

---------- APA ----------
Allegretti, Y.L., Bondar, C., Guzman, L., Cueto Rua, E., Chopita, N., Fuertes, M., Zwirner, N.W.,..., Chirdo, F.G. (2013) . Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease. PLoS ONE, 8(9).
http://dx.doi.org/10.1371/journal.pone.0073658
---------- CHICAGO ----------
Allegretti, Y.L., Bondar, C., Guzman, L., Cueto Rua, E., Chopita, N., Fuertes, M., et al. "Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease" . PLoS ONE 8, no. 9 (2013).
http://dx.doi.org/10.1371/journal.pone.0073658
---------- MLA ----------
Allegretti, Y.L., Bondar, C., Guzman, L., Cueto Rua, E., Chopita, N., Fuertes, M., et al. "Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease" . PLoS ONE, vol. 8, no. 9, 2013.
http://dx.doi.org/10.1371/journal.pone.0073658
---------- VANCOUVER ----------
Allegretti, Y.L., Bondar, C., Guzman, L., Cueto Rua, E., Chopita, N., Fuertes, M., et al. Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease. PLoS ONE. 2013;8(9).
http://dx.doi.org/10.1371/journal.pone.0073658