The CXCR3 / CXCL10 axis. Role in coeliac disease pathogenesis

BONDAR, CONSTANZA; ARAYA, ROMINA; RULLI, EZEQUIEL; GUZMAN, LUCIANA; CUETO RUA, EDUARDO; CHOPITA, NÉSTOR; CHIRDO, FERNANDO

Encuentro; 25th meeting of Working Group on Prolamin Analysis and Toxicity; 2011

Active Coeliac Disease (CD) is characterised by histological changes in the intestinal mucosa, leading to an enteropathy a consequence of both innate and adaptive immunity pathogenic mechanisms. 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. Infiltrating CD4+ T lymphocytes. belong to the Th1 subset, and upon activation abundantly produce IFNγ. Different pairs of receptor/ligand determine the selective migration of lymphocytes in the intestinal mucosa under homeostatic conditions. However, under an inflammatory process, cell recruitment involves other pathways such as the CXCR3/CXCL10 The aim of this work was to assess the role of the CXCL10/ CXCR3 axis in coeliac disease pathogenesis. These observations suggest that the massive production of CXCL10 in the small intestine in active CD may mediate the recruitment and activation of CXCR3+ cells. This is the first report describing the role of CXCR3/CXCL10 axis in the pathogenesis of CD