The association among autoimmunity, chronic inflammation and malignancy has been described and confirmed by epidemiological studies. Notwithstanding these achievements, the molecular mechanisms underlying this association are still unknown. Several evidences suggest that patients suffering from Systemic Lupus Erythematosus, Rheumatoid Arthritis and Sjogren’s Syndrome are prone to develop B-cell Non-Hodgkin’s Lymphomas. We investigated the role of Tir8/Sigirr gene, already known to be associated with autoimmunity, in the development of lymphoma. Indeed, the ability to dampen signaling from IL-1R and TLR family members confers TIR8/SIGIRR the ability to act as regulator of inflammation, cancer-related inflammation and autoimmunity. In this study we describe the occurrence of B-cell lymphoma in B6lpr/lpr and B6lpr/lpr/Tir8−/− mice. Both strains developed Diffuse Large B-Cell Lymphoma (DLBCL) during their late age, but in B6lpr/lpr/Tir8−/− mice DLBCL occurred earlier (10-12 months vs 15-18 months) and were more aggressive, with significantly higher mortality (100% vs 22%, respectively in 15 months old B6lpr/lpr/Tir8−/− and B6lpr/lpr mice). Histopathologic analysis of spleen and lymph nodes of B6lpr/lpr/Tir8−/− mice documented clear-cut DLBCL areas arising within a context of atypical lymphoproliferative disorder; these results were corroborated by both molecular analysis and transplantation experiments. Clonal rearrangement was present in both strains. However, only recipients of spleen or lymph node cell suspensions collected from B6lpr/lpr/Tir8−/− mice developed DLBCL. These observations unveil a role of TIR8 in the occurrence and development of DLBCL, suggesting its potential role in targeted therapy. Moreover, the B6lpr/lpr/Tir8−/− mouse could be a model to establish and evaluate studies of novel therapeutic protocols in DLBCL.
|Titolo:||LPR mice with TIR8 deficiency are prone to develop B-cell lymphomas|
RIVA, FEDERICA (Primo)
|Data di pubblicazione:||set-2014|
|Settore Scientifico Disciplinare:||Settore VET/05 - Malattie Infettive degli Animali Domestici|
|Citazione:||LPR mice with TIR8 deficiency are prone to develop B-cell lymphomas / F. Riva, M. Ponzoni, S. Bertilaccio, N. Polentarutti, A. Anselmo, A. Innocenzi, F. Caligaris-Cappio, A. Mantovani, M. Muzio, C. Garlanda. ((Intervento presentato al 3. convegno Conference of translational medicine on pathogenesis and therapy of immune-mediated diseases tenutosi a Milano nel 2014.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|