IL-1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development

Chronic inflammation, including that driven by autoimmunity, is associated with development of B-cell lymphomas. IL-1R8 is a regulatory receptor belonging to the IL-1R family, which negatively regulates NF-κB activation following stimulation of IL-1R or Toll Like Receptor (TLR) family members. IL-1R8-deficiency is associated with the development of severe autoimmune lupus-like disease in lpr mice. We herein asked if concomitant exacerbated inflammation and autoimmunity caused by the deficiency of IL-1R8 could recapitulate autoimmunity-associated lymphomagenesis. We thus monitored B-cell lymphoma development during aging of IL-1R8-deficient lpr mice, observing increased lymphoid cell expansion that evolved to Diffuse Large B-cell Lymphoma (DLBCL). Molecular and gene expression analysis showed that the NF-κB pathway was constitutively activated in Il1r8 -/- / lpr B-splenocytes. In human DLBCL, IL-1R8 was expressed at low levels compared to normal B cells and higher IL-1R8 expression was associated with better outcome. Thus, IL-1R8 silencing is associated with increased lymphoproliferation and transformation in the pathogenesis of B cell lymphomas associated to autoimmunity.