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. 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.
Laboratorio de Investigación en el Sistema Inmune - LISIN, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina.
Yessica L
YL
Allegretti
Constanza
C
Bondar
Luciana
L
Guzman
Eduardo
E
Cueto Rua
Nestor
N
Chopita
Mercedes
M
Fuertes
Norberto W
NW
Zwirner
Fernando G
FG
Chirdo
D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002446:Celiac Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology; D020895:Enterocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013312:Stress, Physiological / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen