Celiac disease pathogenesis: the proinflammatory cytokine network.
In susceptible individuals, the adaptive response, mediated by the activation of antigen-specific T lymphocytes, drives a proinflammatory response, which ends in an immune-mediated enteropathy characterized by villous atrophy, crypt hyperplasia, and recruitment of intraepithelial lymphocytes. In addition, some gluten peptides are able to induce an innate immune response in intestinal mucosa. The molecular mechanisms and the cells involved in the initial stages of the gluten-intestinal mucosa interaction are poorly understood to date. There is evidence of a direct toxic effect of gluten peptides in several biological models. However, the failure to control the inflammatory response may be one of the factors underlying gluten intolerance in these individuals. The cytokine network involved in celiac disease is characterized by abundant interferon-gamma in the intestinal mucosa. In addition, the production of interleukin (IL)-15, IL-18, and IL-21 is linked to gluten intake, which can drive the inflammatory response probably sustained by IL-18, IL-21, and perhaps IL-27 through STAT1 and STAT5 pathways, whereas neither IL-12 nor IL-23 plays a significant role in pathogenic mechanisms. Herein we describe the involvement of these activation pathways in the context of the pathogenesis of celiac disease.
Garrote
José Antonio
JA
Mucosal Immunity Group, Instituto de Biología y Genética Molecular, Universidad de Valladolid-CSIC, Spain. jgarrote@hcuv.sacyl.es
Gómez-González
Emma
E
Bernardo
David
D
Arranz
Eduardo
E
Chirdo
Fernando
F
D002446:Celiac Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005903:Gliadin / Q000276:immunology; D005983:Glutens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007223:Infant; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D018836:Inflammation Mediators; D005983:Glutens; D005903:Gliadin