TY - JOUR
T1 - IL1R8 deficiency drives autoimmunity-associated lymphoma development
AU - Riva, Federica
AU - Ponzoni, Maurilio
AU - Supino, Domenico
AU - Bertilaccio, Maria Teresa Sabrina
AU - Polentarutti, Nadia
AU - Massara, Matteo
AU - Pasqualini, Fabio
AU - Carriero, Roberta
AU - Innocenzi, Anna
AU - Anselmo, Achille
AU - Veliz-Rodriguez, Tania
AU - Simonetti, Giorgia
AU - Anders, Hans Joachim
AU - Caligaris-Cappio, Federico
AU - Mantovani, Alberto
AU - Muzio, Marta
AU - Garlanda, Cecilia
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/6
Y1 - 2019/6
N2 - 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-κB 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 development 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-κB 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.
AB - 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-κB 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 development 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-κB 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.
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U2 - 10.1158/2326-6066.CIR-18-0698
DO - 10.1158/2326-6066.CIR-18-0698
M3 - Article
C2 - 31018956
AN - SCOPUS:85067219905
SN - 2326-6066
VL - 7
SP - 874
EP - 885
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 6
ER -