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Crohn's disease and upregulated IL-12R?2
Arthritis Research & Therapy volume 3, Article number: 66879 (2001)
Much evidence indicates that activated Th1 cells play an important role in the pathogenesis of tissue damage in Crohn's disease (CD). Interleukin (IL)-12 is known to direct Th cells toward a Th1 pathway. Th1 cells express both the ?1 and the ?2 subunits of the IL-12 receptor (IL-12R). IL-12R?2 chain is the signaling component of IL-12R, and it directly interacts with STAT4. Knowing that neutralization of IL-12 leads to complete recovery of an experimental colitis model resembling CD, the authors studied IL-12R expression in human gastrointestinal mucosa of patients with various gastrointestinal diseases, including CD.
Expression of IL-12R?2 mRNA expression was increased in active CD, Helicobacter pylori (HP)-associated gastritis, and salmonella colitis when compared with expression in inactive CD, ulcerative colitis, noninflammatory controls, and celiac disease. In contrast, IL-12R?1 expression was identical in these gastrointestinal diseases. In CD, IL-12R?2 expression strictly correlated with tyrosine phosphorylation of STAT4 and interferon (IFN)-? expression. Finally, IL-12 enhanced IL-12R?2 mRNA expression in normal lamina propria mononuclear cells. Taken together, these results suggest that an increase of IL-12R?2 mRNA expression may contribute to the polarization of the Th1-type cytokine profile in CD.
These results suggest that an increase of IL-12R?2 expression induced by IL-12 may be responsible for the maintenance of the inflammatory process in CD. Moreover, the increase of IL-12R?2 expression in bacterial gastrointestinal disease such as HP-associated gastritis or salmonella colitis suggests that bacteria and bacterial components may contribute to modulation of IL-12R?2 levels. This observation adds further support to a link between inflammatory diseases and bacterial infection.
Parrello T, Monteleone G, Cucchiara S, Monteleone I, Sebkova L, Doldo P, Luzza F, Pallone F: Upregulation of the IL-12 receptor ?2 chain in Crohn's disease. J Immunol . 2001, 165: 7234-7239.
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Fournel, S. Crohn's disease and upregulated IL-12R?2. Arthritis Res Ther 3, 66879 (2001) doi:10.1186/ar-2001-66879
- Crohn's disease
- gastrointestinal inflammatory disease