Data di Pubblicazione:
2013
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 - In: 15th International Congress of Immunology: Immunitas vis naturae[s.l] : The Editors, 2013 Aug. - pp. 318 (( Intervento presentato al 15. convegno 15th International Congress of Immunology tenutosi a Milano nel 2013.
Abstract:
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, cancerrelated
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 B6 lpr/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.
Tipologia IRIS:
03 - Contributo in volume
Elenco autori:
F. Riva, M. Ponzoni, S. Bertilaccio, N. Polentarutti, A. Anselmo, A. Innocenzi, F. Caligaris Cappio, A. Mantovani, M. Muzio, C. Garlanda
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Titolo del libro:
15th International Congress of Immunology: Immunitas vis naturae