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)

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 Kurowska-Stolarska, Professor Mariola and Elmesmari, Dr Aziza 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 > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Nature Communications 7:12970
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
51411	1	MicroRNA in monocytes: its contribution to the pathogenesis of arthritis and cardiovascular co-morbidity	Mariola Kurowska-Stolarska	Arthritis Research UK (ARC)	19213	III -IMMUNOLOGY