Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models

Maria Teresa Sabrina Bertilaccio, Giorgia Simonetti, Antonis Dagklis, Martina Rocchi, Tania Veliz Rodriguez, Benedetta Apollonio, Alberto Mantovani, Maurilio Ponzoni, Paolo Ghia, Cecilia Garlanda, Federico Caligaris-Cappio, Marta Muzio

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Inflammation is involved in the initiation and progression of several chronic lymphoid malignancies of B-cell type. Tolllike receptors (TLR) are transmembrane inflammatory receptors that on recognition of pathogen-associated molecular patterns trigger an innate immune response and bridge the innate and adaptive immune response by acting as costimulatory signals for B cells. Fine tuning of TLR and IL-1R-like (ILR) activity is regulated by TIR8 (SIGIRR), a transmembrane receptor of the TLR/ILR family which inhibits other family members. To test the hypothesis that TLR and/or ILR may play a role in the natural history of chronic B-cell tumors, we crossed Eμ-TCL1 transgenic mice, a well established model of chronic lymphocytic leukemia (CLL), with mice lacking the inhibitory receptor TIR8 that allow an unabated TLR-mediated stimulation. We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened. The morphology and phenotype of the mouse leukemic expansions reproduce the progression of human CLL into an aggressive and frequently terminal phase characterized by the appearance of prolymphocytes. This study reveals an important pathogenetic implication of TLR in CLL development and progression.

Original languageEnglish
Pages (from-to)660-669
Number of pages10
JournalBlood
Volume118
Issue number3
DOIs
Publication statusPublished - Jul 21 2011

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B-Cell Chronic Lymphocytic Leukemia
B-Lymphocytes
Cells
Innate Immunity
Adaptive Immunity
Natural History
Transgenic Mice
Tumors
Neoplasms
Tuning
Inflammation
Phenotype

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Bertilaccio, M. T. S., Simonetti, G., Dagklis, A., Rocchi, M., Rodriguez, T. V., Apollonio, B., ... Muzio, M. (2011). Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models. Blood, 118(3), 660-669. https://doi.org/10.1182/blood-2011-01-329870

Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models. / Bertilaccio, Maria Teresa Sabrina; Simonetti, Giorgia; Dagklis, Antonis; Rocchi, Martina; Rodriguez, Tania Veliz; Apollonio, Benedetta; Mantovani, Alberto; Ponzoni, Maurilio; Ghia, Paolo; Garlanda, Cecilia; Caligaris-Cappio, Federico; Muzio, Marta.

In: Blood, Vol. 118, No. 3, 21.07.2011, p. 660-669.

Research output: Contribution to journalArticle

Bertilaccio, MTS, Simonetti, G, Dagklis, A, Rocchi, M, Rodriguez, TV, Apollonio, B, Mantovani, A, Ponzoni, M, Ghia, P, Garlanda, C, Caligaris-Cappio, F & Muzio, M 2011, 'Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models', Blood, vol. 118, no. 3, pp. 660-669. https://doi.org/10.1182/blood-2011-01-329870
Bertilaccio MTS, Simonetti G, Dagklis A, Rocchi M, Rodriguez TV, Apollonio B et al. Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models. Blood. 2011 Jul 21;118(3):660-669. https://doi.org/10.1182/blood-2011-01-329870
Bertilaccio, Maria Teresa Sabrina ; Simonetti, Giorgia ; Dagklis, Antonis ; Rocchi, Martina ; Rodriguez, Tania Veliz ; Apollonio, Benedetta ; Mantovani, Alberto ; Ponzoni, Maurilio ; Ghia, Paolo ; Garlanda, Cecilia ; Caligaris-Cappio, Federico ; Muzio, Marta. / Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models. In: Blood. 2011 ; Vol. 118, No. 3. pp. 660-669.
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