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Arthritis Research & Therapy

Open Access

Crohn's disease and upregulated IL-12R?2

  • Sylvie Fournel1
Arthritis Research & Therapy20013:66879

https://doi.org/10.1186/ar-2001-66879

Published: 25 January 2001

Keywords

Crohn's diseaseIL-12Rgastrointestinal inflammatory disease

Context

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.

Significant findings

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.

Comments

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.

Methods

PCR

Authors’ Affiliations

(1)
CNRS, Strasbourg, France

References

  1. 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.View ArticleGoogle Scholar

Copyright

© Biomed Central Ltd 2001

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