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

Alivernini, S. et al. (2016) MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis. Nature Communications, 7, 12970. (doi:10.1038/ncomms12970) (PMID:27671860) (PMCID:PMC5052655)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Elmesmari, Dr Aziza and Kurowska-Stolarska, Dr Mariola and Alivernini, Mr Stefano
Authors: 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., and Ferraccioli, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Published Online:27 September 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Nature Communications 7:12970
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
514111MicroRNA in monocytes: its contribution to the pathogenesis of arthritis and cardiovascular co-morbidityMariola Kurowska-StolarskaArthritis Research UK (ARC)19213III -IMMUNOLOGY