Chronic inflammation, including that driven by autoimmunity, is associated with 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 (TLR) 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 aging of IL1R8-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, IL1R8 had reduced expression compared to normal B cells, and higher IL1R8 expression was associated with better outcome. Thus, IL1R8 silencing is associated with increased lymphoproliferation and transformation in the pathogenesis of B-cell lymphomas associated with autoimmunity.
IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development / F. Riva, M. Ponzoni, D. Supino, M.T.S. Bertilaccio, N. Polentarutti, M. Massara, F. Pasqualini, R. Carriero, A. Innocenzi, A. Anselmo, T. Veliz Rodriguez, G. Simonetti, H. Anders, F. Caligaris Cappio, A. Mantovani, M. Muzio, C. Garlanda. - In: CANCER IMMUNOLOGY RESEARCH. - ISSN 2326-6066. - 7:6(2019 Jun), pp. 874-885.
|Titolo:||IL1R8 Deficiency Drives Autoimmunity-Associated Lymphoma Development|
RIVA, FEDERICA (Primo)
|Settore Scientifico Disciplinare:||Settore VET/03 - Patologia Generale e Anatomia Patologica Veterinaria|
Settore VET/05 - Malattie Infettive degli Animali Domestici
Settore MED/04 - Patologia Generale
|Data di pubblicazione:||giu-2019|
|Data ahead of print / Data di stampa:||24-apr-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1158/2326-6066.CIR-18-0698|
|Appare nelle tipologie:||01 - Articolo su periodico|