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

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. Particul...

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Guardado en:
Detalles Bibliográficos
Publicado: 2013
Materias:
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
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n9_p_Allegretti
http://hdl.handle.net/20.500.12110/paper_19326203_v8_n9_p_Allegretti
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

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