MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis.
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.
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Stefano
S
Alivernini
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Mariola
M
Kurowska-Stolarska
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Barbara
B
Tolusso
Division of Pathology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Roberta
R
Benvenuto
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Aziza
A
Elmesmari
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Silvia
S
Canestri
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Luca
L
Petricca
Division of Pathology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Antonella
A
Mangoni
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Anna Laura
AL
Fedele
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.|Division of Pathology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Clara
C
Di Mario
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Maria Rita
MR
Gigante
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Elisa
E
Gremese
Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Iain B
IB
McInnes
Division of Rheumatology, Fondazione Policlinico Universitario A. Gemelli, Catholic University of the Sacred Heart, Rome 00168, Italy.
Gianfranco
G
Ferraccioli
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
D007072:Immunoglobulin D; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000099232:Proto-Oncogene Protein Spi-1; C524942:MIRN155 microRNA, human
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