CXCR3 / CXCL10 axis in intestinal mucosa in active Coeliac Disease

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

Leuven

Congreso; 26th Meeting of the European Working Group on Prolamin Analysis and Toxicity.; 2012

European Working Group on Prolamin Analysis and Toxicity.

Coeliac disease (CD) is a chronic small intestinal inflammatory condition induced by an inappropriate immune response to dietary gluten. Priming of gluten-specific naive T cells occurs in organised lymphoid tissue, likely in the mesenteric lymph nodes, whereas the activation and expansion of these cells take place in the small intestine lamina propria by antigen presenting cells. Majority of gluten specific T cells are Th1 cells, and consequently IFN producers [1]. Lamina propria also contains a high number of plasma cells, most of them producing anti-TG2 antibodies [2]. Therefore, lymphocytic infiltration mainly composed by CD4+ Th1 cells and plasma cells is one of the chararacteristic findings in intestinal mucosa in active CD. The increased number of lymphoid cells is a consequence of local expansion and/or a specific cell recruitment. Cell migration into the small intestine mucosa requieres different signals from two main systems that guide this process. Expression of adhesion molecules in the endothelial cells, the best example is MadCAM1, and the expression of 47 in lymphoid cells allow the migration of cells out of the blood vessels into the tissue [3]. Inside the tissue, chemokines guide the cells to the site of inflammation. The CXCL10/CXCR3 axis is one of the main factors controlling the cell recruitment under an inflammatory process, as it was reported for chronic inflammatory process such as autoimmunity (type 1 diabetes, reumatoid arthritis)[4, 5]. IFNis the stronger inducer of CXCL10 expression. CXCL10 is produced by CD4+ T cells, NK and NKT cells, monocytes, dendritic cells, neutrophils, fibroblasts [6]. Remarkably, synoviocytes and cells, actively produce CXCL10 during the inflammatory process, arthritis or insulitis, respectively [5]. CXCL10 interacts with CXCR3, which is expressed by T lymphocytes, NK cells, eosinophils, monocytes, B lymphocytes, plasma cells. Particularly, Th1 cells are CXCR3+ cells [6].