MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD - CD27 - memory B-cell population in ACPA + RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-α, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA.

Alivernini, S., Kurowska Stolarska, M., Tolusso, B., Benvenuto, R., Elmesmari, A., Canestri, S., Petricca, L., Mangoni, A., Fedele, A. L., Di Mario, C., Gigante, M. R., Gremese, E., Mcinnes, I. B., Ferraccioli, G., MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis, <<NATURE COMMUNICATIONS>>, 2016; 7 (N/A): 12970-N/A. [doi:10.1038/ncomms12970] [http://hdl.handle.net/10807/94038]

MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis

Alivernini, Stefano
Primo
;
Tolusso, Barbara;Petricca, Luca;Fedele, Anna Laura;Di Mario, Clara;Gigante, Maria Rita;Gremese, Elisa;Ferraccioli, Gianfranco
2016

Abstract

MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD - CD27 - memory B-cell population in ACPA + RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-α, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA.
Inglese
Alivernini, S., Kurowska Stolarska, M., Tolusso, B., Benvenuto, R., Elmesmari, A., Canestri, S., Petricca, L., Mangoni, A., Fedele, A. L., Di Mario, C., Gigante, M. R., Gremese, E., Mcinnes, I. B., Ferraccioli, G., MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis, <<NATURE COMMUNICATIONS>>, 2016; 7 (N/A): 12970-N/A. [doi:10.1038/ncomms12970] [http://hdl.handle.net/10807/94038]
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