IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development

Federica Riva, Maurilio Ponzoni, Domenico Supino, Maria Teresa Sabrina Bertilaccio, Nadia Polentarutti, Matteo Massara, Fabio Pasqualini, Roberta Carriero, Anna Innocenzi, Achille Anselmo, Tania Veliz-Rodriguez, Giorgia Simonetti, Hans-Joachim Anders, Federico Caligaris-Cappio, Alberto Mantovani, Marta Muzio, Cecilia Garlanda

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)874-885
Number of pages12
JournalCancer immunology research
Issue number6
Publication statusPublished - Jun 2019


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