Expression of a splice variant of CXCR3 in Crohn's disease patients; indication for a lymphocyte—epithelial cell interaction

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Abstract

Background and Aim

T-lymphocyte migration is implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). CXC chemokines MIG, IP-10, and I-TAC act by binding to CXCR3 receptor on T-lymphocytes. We investigated the role of these chemokines and their receptor in patients with UC, CD, and normal controls (NC).

Methods

Chemokine expression and serum levels were examined in colonic biopsies from patients and NC using reverse transcription–polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. HT-29 and Caco2 colonic epithelial cells were studied following in vitro stimulation with proinflammatory (Th1) and Th2-derived cytokines. CXCR3 receptor expression was assessed in CD3+ peripheral blood lymphocytes (PBL) from patients and NC and in stimulated Jurkat leukaemia cells, using RT-PCR and flow cytometry.

Results

Full size CXCR3 mRNA (FS) expression was found in CD3+ PBL from controls and UC, but not from CD patients. In contrast, CD3+ PBL from CD patients showed a marked mRNA expression of the spliced variant CXCR3 (TV). This finding explains the high expression of CXCR3 on CD3+ PBL from CD patients in flow cytometry. Increased chemokine expression and production was found in colonic biopsies and serum from CD compared to UC patients and controls. Stimulation of epithelial cells with proinflammatory cytokines significantly induced chemokine production. The addition of Th2 cytokines had an inhibitory effect. Stimulation of Jurkat cells with cytokines and supernatant conditioned media from epithelial cells induced CXCR3TV expression.

Conclusions

These data demonstrate that PBL from CD patients express a spliced variant of the CXCR3 receptor and suggest a role for the colonic epithelial cells in T-lymphocyte migration in intestinal inflammation.

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