title: 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.
authors.affiliation: Department of Gastroenterology, Translational Research Centre for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium. Clementine.Perrier@med.kuleuven.be
authors.forename: Clémentine
authors.initials: C
authors.lastname: Perrier
authors.forename: Ingrid
authors.initials: I
authors.lastname: Arijs
authors.forename: Dominiek
authors.initials: D
authors.lastname: Staelens
authors.forename: Christine
authors.initials: C
authors.lastname: Breynaert
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cleynen
authors.forename: Kris
authors.initials: K
authors.lastname: Covens
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Gert
authors.initials: G
authors.lastname: de Hertogh
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Jan L
authors.initials: JL
authors.lastname: Ceuppens
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy; D000069285:Infliximab; D053720:Interleukin-15 Receptor alpha Subunit / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D053720:Interleukin-15 Receptor alpha Subunit; D012333:RNA, Messenger; D000069285:Infliximab