| Abstract |
Chemokines and their receptors have emerged as critical regulators of leukocyte trafficking during infection and inflammation. At least 40 chemokines and 19 chemokine receptors have been described in humans. The combinatorial expression of chemokine receptors on the cell surface of leukocytes provides cues to migratory signals through chemokine gradients, which provide high selectivity and specificity in the type and activation state of the recruited cells. Several homeostatic chemokines function as regulators of basal lymphocyte trafficking to or within lymphoid organs and in peripheral tissues, whereas the inflammatory ones are involved in the recruitment of immune cells to the site of inflammation. Some constitutively expressed chemokines and their receptors are involved in the organization and compartmentalization of immune responses to distinct anatomic locations. Examples include the association of the CTACK/CCL27 and its receptor CCR10 and TECK/CCL25 and its receptor CCR9 with skin and small intestinal mucosal immune responses, respectively. We studied the role of ΤECK/CCL25 and its receptor CCR9 in mucosal immunity and its possible role in the pathogenesis of human small intestinal Crohns disease (CD). Expression patterns of TECK/CCL25 were analyzed by immunohistochemistry in normal mucosal tissues and compared with that in inflamed small and large intestine. The expression patterns of CCR9 in T lymphocytes in mucosal lymphoid tissues and peripheral blood were analyzed in normal controls and patients with small intestinal or colonic inflammation. Finally the phenotypic and functional characteristics of the small number of CCR9+ T lymphocytes from peripheral blood of healthy normal donors were analyzed. Our results showed that TECK/CCL25 is selectively expressed in the small intestine but not colon and its expression is increased in small intestinal but not colonic CD. TECK/CCL25 chemoattracts small intestinal, but not colonic, lymphocytes through the chemokine receptor CCR9. CCR9+ T lymphocytes are preferentially localized to the small intestinal immune compartment and their percentage is increased in the peripheral circulation of patients with small intestinal inflammatory diseases, such as CD and celiac disease. The small percentage of CCR9+ T lymphocytes isolated from the peripheral blood of healthy donors have an activated phenotype, a T helper 1 (Th1) and T regulatory 1 (Tr1) cytokine profile and provide B cell help for immunoglobulin, including IgA, production, and hence have mucosal T cell characteristics. In conclusion, the chemokine TECK/CCL25 and its receptor CCR9 characterize the small intestinal immune compartment. Alterations of TECK/CCL25 and CCR9 expression in small intestinal CD imply an important role of this chemokine ligand/receptor pair in the pathogenesis of small intestinal CD.
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Ο ρόλος της χημειοκίνης TECK (THYMUS-EXPRESSED CHEMOKINE)/CCL25 και του χημειοϋποδοχέα CCR9 στην παθογένεια της νόσου του CROHN στο λεπτό έντερο
