IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development

Riva, Federica; Ponzoni, Maurilio; Supino, Domenico; Bertilaccio, Maria Teresa Sabrina; Polentarutti, Nadia; Massara, Matteo; Pasqualini, Fabio; Carriero, Roberta; Innocenzi, Anna; Anselmo, Achille; Veliz-Rodriguez, Tania; Simonetti, Giorgia; Anders, Hans-Joachim; Caligaris-Cappio, Federico; Mantovani, Alberto; Muzio, Marta und Garlanda, Cecilia (2019): IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development. In: Cancer Immunology Research, Bd. 7, Nr. 6: S. 874-885

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-kB 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 devel-opment 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-kB 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2326-6066
• Sprache: Englisch