title: Interleukin 22 signaling promotes cell growth in mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) is a specific type of aggressive B-cell non-Hodgkin lymphoma. We recently found that IL-22RA1, one of the two subunits of the interleukin 22 (IL-22) receptor, is expressed in MCL cell lines but not benign lymphocytes. In view of normal functions of IL-22 signaling, we hypothesized that the aberrant expression of IL-22RA1 may contribute to the deregulation of various cell signaling pathways, thereby promoting cell growth in MCL. In this study, we first demonstrated the expression of IL-22RA1 in all three MCL cell lines and eight frozen tumors examined using reverse transcription-polymerase chain reaction and Western blot analysis. In support of the concept that IL-22 signaling is biologically important in MCL, we found that MCL cells treated with recombinant IL-22 had a significant increase in cell growth that was associated with STAT3 activation. To investigate the mechanism underlying the aberrant expression of IL-22RA1, we analyzed the gene promoter of IL-22RA1, and we found multiple binding sites for NF-κB, a transcriptional factor strongly implicated in the pathogenesis of MCL. Pharmacologic inhibition of NF-κB resulted in a substantial reduction in the level of IL-22RA1 protein expression in MCL cells. To conclude, IL-22RA is aberrantly expressed in MCL, and we have provided evidence that IL-22 signaling contributes to the pathogenesis of MCL.
authors.affiliation: Department of Laboratory Medicine and Pathology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Pascal
authors.initials: P
authors.lastname: Gelebart
authors.forename: Zoulika
authors.initials: Z
authors.lastname: Zak
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dien-Bard
authors.forename: Mona
authors.initials: M
authors.lastname: Anand
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai