Expression of the T-Cell Chemoattractant Chemokine Lymphotactin in Crohn’s Disease

Abstract

Recruitment of lymphocytes is a prominent feature of the inflammatory process in Crohn's disease (CD). The present study was undertaken to investigate the expression of the novel lymphocyte-specific chemoattractant lymphotactin (Lptn) as a potential regulatory factor for the recruitment of T cells in CD. The expression of Lptn mRNA was quantified in resection specimens of patients with CD in comparison to normal controls without signs of inflammation by real-time quantitative reverse transcriptase-polymerase chain reaction and localized by nonradioactive in situ hybridization. Furthermore, the phenotype of cells expressing Lptn mRNA was characterized. In contrast to normal controls Lptn mRNA was significantly increased in tissue samples affected by CD. Cells expressing Lptn were identified as T cells, mast cells, and unexpectedly dendritic cells. Lptn mRNA was found to be up-regulated on stimulation with phorbol-12-myristate-13-acetate and concanavalin A in T cells isolated from peripheral blood, which could be prevented by dexamethasone, cyclosporine A, and FK506. A similar regulation mechanism could be identified for the Lptn receptor GPR-5 in peripheral T cells. In addition, Lptn mRNA expression could be induced in mature monocyte-derived dendritic cells. 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 regulator for lymphocyte trafficking and maintenance of the inflammatory process observed in CD, which might be partly mediated through an autocrine/paracrine pathway of activated T cells.

γδ T Cells Respond Directly to Pathogen-Associated Molecular Patterns

“…Mutations in NOD2 that disrupt its signaling through NFB have been associated with Crohn's disease, a type of inflammatory bowel disease (53,54). An increase in expression of lymphotactin in Crohn's disease was also reported, but the specific role of ␥␦ T cells was not addressed in this study (55). Our data suggest that NOD2 mRNA is expressed in human ␥␦ T cells and may be in part responsible for the reaction to PAMPs that is distinct from that of monocytes.…”

Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease

“…Predominantly produced by activated Th1 CD4 þ , CD8 þ T cells and NK cells, 71,72 XCL1 ligation to its receptor XCR1 not only induces T and NK cell recruitment and co-activates macrophages but also can increase regulatory T-cell function, suppress the IFNg production of CD4 þ T cells and seems to be involved in organ rejection. 71,[73][74][75][76][77][78] Increased levels of XCL1 have been reported in the bronchoalveolar lavage fluid of mice suffering from idiopathic pneumonia syndrome after allogeneic BMT, 79 and antigen priming of CTLs was enhanced in the presence of XCL1. 80 Therefore, it can be speculated, that XCL1-XCR1 interactions can promote the inflammatory process of aGVHD through an autocrine or a paracrine pathway or potentially mediate a downregulation of inflammation through regulatory and tolerogenic effects.…”

The Lymphotactin Receptor Is Expressed in Epithelial Ovarian Carcinoma and Contributes to Cell Migration and Proliferation

“…As recently shown, XCR1-positive thymic dendritic cells were attracted into medulla by XCL1-positive medullary thymic epithelial cells in vivo (20). The XCL1-XCR1 axis contributes to the progression of various diseases, including rheumatoid arthritis (21), Crohn disease (22), and many others (23). The role of XCL1-XCR1 in cell proliferation, migration, and invasion has been reported in a carcinoma of epithelial origin and an oral squamous carcinoma (24).…”