Interleukin‐15 receptor α expression in inflammatory bowel disease patients before and after normalization of inflammation with infliximab

Abstract

Interleukin-15 (IL-15) is a pro-inflammatory cytokine thought to contribute to the inflammation in inflammatory bowel diseases (IBD). The specific receptor chain IL-15Rα can be expressed as a transmembranous signalling receptor, or can be cleaved by a disintegrin and metalloprotease domain 17 (ADAM17) into a neutralizing, soluble receptor (sIL-15Rα). The aim of this study is to evaluate the expression of IL-15Rα in ulcerative colitis (UC) and Crohn's disease (CD) patients before and after infliximab (IFX) therapy. Gene expression of IL-15Rα, IL-15 and ADAM17 was measured at the mRNA level by quantitative reverse transcription-PCR in mucosal biopsies harvested before and after first IFX therapy. Concentrations of sIL-15Rα were measured in sera of patients by ELISA and IL-15Rα protein was localized in the gut by immunohistochemistry and immunofluorescence. Mucosal expression of IL-15Rα is increased in UC and CD patients compared with controls and it remains elevated after IFX therapy in both responder and non-responder patients. The concentration of sIL-15Rα in serum is also increased in UC patients when compared with controls and does not differ between responders and non-responders either before or after IFX. CD patients have levels of sIL-15Rα comparable to healthy controls before and after therapy. In mucosal tissues, IL-15Rα(+) cells closely resemble activated memory B cells with a pre-plasmablastic phenotype. To conclude, IBD patients have an increased expression of IL-15Rα mRNA in the mucosa. Expression is localized in B cells, suggesting that IL-15 regulates B-cell functions during bowel inflammation. No change in release of sIL-15Rα is observed in patients treated with IFX.