Expression of the T-cell chemoattractant chemokine lymphotactin in Crohn'sdisease

Recruitment of lymphocytes is a prominent feature of the inflammatory proce ss In Crohn's disease (CD). The present study was undertaken to investigate the expression of the novel lymphocyte-specific chemoattractant lymphotact in (Lptn) as a potential regulatory factor for the recruitment of T cells i n CD. The expression of Lptn mRNA was quantified in resection specimens of patients with CD in comparison to normal controls without signs of inflamma tion by realtime quantitative reverse transcriptase-polymerase chain reacti on and localized by nonradioactive in situ hybridization. Furthermore, the phenotype of cells expressing Lptn mRNA was characterized. In contrast to n ormal controls Lptn mRNA was significantly increased in tissue samples affe cted by CD. Cells expressing Lptn were identified as T cells, mast cells, a nd unexpectedly dendritic cells. Lptn mRNA was found to be up-regulated on stimulation with phorbol-12-myristate-13-acetate and concanavalin A in T ce lls isolated from peripheral blood, which could be prevented by dexamethaso ne, cyclosporine A, and FK506. A similar regulation mechanism could be iden tified for the Lptn receptor GPR-5 in peripheral T cells. in addition, Lptn mRNA expression could be induced in mature monocyte-derived dendritic cell s. The results indicate that local expression of Lptn by activated T cells and to a lesser extent by mast cells and dendritic cells represents a key r egulator for lymphocyte trafficking and maintenance of the inflammatory pro cess observed in CD, which might be partly mediated through an autocrine/pa racrine pathway of activated T cells.