The CXCR3 / CXCL10 axis. Role in coeliac disease pathogenesis

BONDAR C; ARAYA R; RULLI E; GUZMAN L; CUETO RUA E; CHOPITA N; CHIRDO F

Felbach

Congreso; 25th Meeting of the European Working Group on Prolamin Analysis and Toxicity.; 2011

European Working Group on Prolamin Analysis and Toxicity.

Active Coeliac Disease (CD) is characterised by histological changes in the intestinal mucosa, being the enteropathy a consequence of both innate and adaptive immunity pathogenic mechanisms. Gliadin peptides are able to induce a rapid response in the epithelia and lamina propria involving different inflammatory mediators. Particularly, p31-43 -gliadin peptide has been the most commonly used peptide to assess the innate mechanisms elicited in the intestinal mucosa (Abadie V. et al., 2011). Early pathogenic events involve changes such as disruption of tight junction integrity and the production of proinflammatory cytokines, among them, IL-15 plays a major role at the initial stage. The induction of innate immunity trigger inflammatory mechanisms which could sustain the chronic process, characterised by a massive T and B lymphocyte infiltration in the intestinal mucosa of untreated patients (Meresse B. et al., 2009). It has been clearly established, that gliadins and glutenins peptides activate lamina propria HLA-DQ2/DQ8 restricted -CD4+ T lymphocytes. These T cells, belong to the Th1 subset, and upon activation abundantly produce IFN. Th1 cells are likely activated in mesenteric lymph nodes, circulate in the peripheral blood and then entry in the lamina propria. Migration of cells is governed by a sophisticated system of chemokines and their receptors. Different pairs of receptor/ligand determine the selective migration of lymphocytes in the intestinal mucosa under homeostatic conditions, such as MadCAM1/47 and CCL25/CCR9 (Gorfu G. et al, 2009). However, under an inflammatory process, cell recruitment involves other pathways such as the CXCR3/ CXCL10 axis, which was pointed out as one of the most relevant promoting the arrival of cells to the inflammed tissues. This axis was involved in chronic inflammatory process such as autoimmunity (type 1 diabetes, reumatoid arthritis)(Lee E. Y. et al. 2009; Lacotte S. et al., 2009).