IL1R8 deficiency drives autoimmunity-associated lymphoma development: Cancer Immunology Research

F Riva, M Ponzoni, D Supino, MTS Bertilaccio, N Polentarutti, M Massara, F Pasqualini, R Carriero, A Innocenzi, A Anselmo, T Veliz-Rodriguez, G Simonetti, HJ Anders, F Caligaris-Cappio, A Mantovani, M Muzio, C Garlanda

Research output: Contribution to journalArticle

Abstract

Chronic inflammation, including that driven by autoimmunity, is associated with the development of B-cell lymphomas. IL1R8 is a regulatory receptor belonging to the IL1R family, which negatively regulates NF-κB activation following stimulation of IL1R or Toll-like receptor family members. IL1R8 deficiency is associated with the development of severe autoimmune lupus-like disease in lpr mice. We herein investigated whether concomitant exacerbated inflammation and autoimmunity caused by the deficiency of IL1R8 could recapitulate autoimmunity-associated lymphomagenesis. We thus monitored B-cell lymphoma development during the aging of IL1R8-deficient lpr mice, observing an increased lymphoid cell expansion that evolved to diffuse large B-cell lymphoma (DLBCL). Molecular and gene-expression analyses showed that the NF-κB pathway was constitutively activated in Il1r8-/- /lpr B splenocytes. In human DLBCL, IL1R8 had reduced expression compared with normal B cells, and higher IL1R8 expression was associated with a better outcome. Thus, IL1R8 silencing is associated with increased lymphoproliferation and transformation in the pathogenesis of B-cell lymphomas associated with autoimmunity. © 2019 American Association for Cancer Research.
Original languageEnglish
Pages (from-to)874-885
Number of pages12
JournalCancer immunology research
Volume7
Issue number6
DOIs
Publication statusPublished - 2019

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    Riva, F., Ponzoni, M., Supino, D., Bertilaccio, MTS., Polentarutti, N., Massara, M., Pasqualini, F., Carriero, R., Innocenzi, A., Anselmo, A., Veliz-Rodriguez, T., Simonetti, G., Anders, HJ., Caligaris-Cappio, F., Mantovani, A., Muzio, M., & Garlanda, C. (2019). IL1R8 deficiency drives autoimmunity-associated lymphoma development: Cancer Immunology Research. Cancer immunology research, 7(6), 874-885. https://doi.org/10.1158/2326-6066.CIR-18-0698