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

Stefano Alivernini, Mariola Kurowska-Stolarska, Barbara Tolusso, Roberta Benvenuto, Aziza Elmesmari, Silvia Canestri, Luca Petricca, Antonella Mangoni, Anna Laura Fedele, Clara Di Mario, Maria Rita Gigante, Elisa Gremese, Iain B. McInnes and Gianfranco Ferraccioli ()
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Stefano Alivernini: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Mariola Kurowska-Stolarska: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow
Barbara Tolusso: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Roberta Benvenuto: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Aziza Elmesmari: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow
Silvia Canestri: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Luca Petricca: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Antonella Mangoni: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Anna Laura Fedele: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Clara Di Mario: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Maria Rita Gigante: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Elisa Gremese: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart
Iain B. McInnes: Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow
Gianfranco Ferraccioli: Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12970

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