Immune activation genes in inflammatory bowel disease

Abstract

Background: Inflammatory bowel disease is associated with enhanced activation of T cells, but the genes responsible for this state are not well characterized. Methods: T-cell activation genes were studied in peripheral blood and intestinal mucosal mononuclear cells of control, Crohn's disease, and ulcerative colitis patients. Results: In all groups the expression of interleukin-2 (IL-2), IL-2 receptor α (IL-2Rα), and IL-2Rβ messenger RNA (mRNA) was significantly higher in intestinal than circulating cells, and it correlated well with protein levels. Both IL-2Rα and IL-2Rβ mRNA were abundant in mucosal cells, suggesting that a substantial number of them displays high affinity IL-2R. This would explain why intestinal cells proliferate more, express more IL-2 transcripts, and secrete more IL-2 than peripheral cells. Inflammatory bowel disease cells produced similar or higher IL-2Rα and IL-2Rβ mRNA than controls but generated significantly lower IL-2 mRNA. Thus, the reported defect of IL-2 activity in Crohn's disease and ulcerative colitis is probably related to decreased IL-2 transcription. Crohn's disease intestinal cells had the highest expression of IL-2R gene products. This provides a mechanism for their increased response to IL-2 and supports claims that elevated soluble IL-2Rα serum levels reflect gut T-cell hyperactivity in this disease. Conclusions: These findings underscore the importance of T cells in mucosal immunity and indicate that abnormal T-cell activation is intimately associated to the pathogenesis of inflammatory bowel disease.