Coeliac disease pathogenesis. The proinflammatory cytokine network

GARROTE, JA; GOMES-GONSALEZ E; BERNARDO D; ARRANZ E; CHIRDO F

JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION

Lippincott Williams & Wilkin

Lugar: Philadelphia, USA; Año: 2008 p. 27 - 32

0277-2116

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> In susceptible individuals, the adaptative response, mediated by the activation of antigen specific T lymphocytes, drives a proinflammatory response, which ends in an immune-mediated enteropathy characterised by villous atrophy, crypt hyperplasia and recruitment of intraepithelial lymphocyte. 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 yet. There are evidences of the direct toxic effect of gluten peptides in several biological models. However, the failure in controlling the inflammatory response might be one of the factors underlying gluten intolerance in these individuals. The cytokine network involved in coeliac disease is characterised by abundant IFNg in the intestinal mucosa. In addition, production of IL-15, IL-18 and IL-21 are linked to the gluten intake, which can drive the inflammatory response probably sustained by IL-18, IL-21 and perhaps IL-27 through STAT1 and STAT5 pathways, while neither IL-12 nor IL-23 play a significant role in pathogenic mechanisms. Herein we describe the involvement of these activation pathways in the context of the coeliac disease pathogenesis.