Increased expression of interleukin-12 receptor β₂ on lamina propria mononuclear cells of patients with active Crohn's disease

Heading

Abstract

Background and aims. Since interleukin-12 is pathogenetically involved in Crohn's disease (CD) but not in ulcerative colitis (UC), expression and mechanisms of induction of interleukin-12 receptor (IL-12R) subunits β₁ and β₂ were analyzed in lamina propria mononuclear cells (LPMNC) of patients with CD and UC.

Patients and methods. LPMNC from patients with CD (n=17), UC (n=14), and controls (n=19) were isolated by standard techniques. IL-12Rβ₁ and IL-12Rβ₂ transcripts were semiquantified by RT-PCR, and expression of IL-12Rβ₂ chain was characterized by flow cytometry. LPMNC were activated by cross-linking with anti-CD3 antibodies and B7-1 costimulation.

Results. IL-12Rβ₁ and IL-12Rβ₂ transcript concentrations were higher in inflamed specimens than in noninflamed segments of patients with CD but not in UC. Increased percentage of mucosal CD4⁺/IL-12Rβ₂ ⁺ cells was observed in active CD, but not UC. In vitro stimulation of LPMNC with anti-CD3 antibodies resulted in an increase in IL-12Rβ₁ transcripts irrespective of B7-1 mediated costimulation (84% and 95%, respectively). However, increased expression of IL-12Rβ₂ mRNA (110%) was detected only after B7-1 costimulation.

Conclusion. Our data indicate that increased mucosal expression of IL-12Rβ₂ on LPMNC in CD but not in UC may be the result of B7-1 costimulation. Modulation or inhibition of IL-12Rβ₂ expression on LPMNC could provide a selective therapeutic approach in CD.