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

被引：110

作者：

Alivernini, Stefano ^{[1
]}

Kurowska-Stolarska, Mariola ^{[2
]}

Tolusso, Barbara ^{[1
]}

Benvenuto, Roberta ^{[3
]}

Elmesmari, Aziza ^{[2
]}

Canestri, Silvia ^{[1
]}

Petricca, Luca ^{[1
]}

Mangoni, Antonella ^{[3
]}

Fedele, Anna Laura ^{[1
]}

Di Mario, Clara ^{[1
,3
]}

Gigante, Maria Rita ^{[1
]}

Gremese, Elisa ^{[1
]}

McInnes, Iain B. ^{[2
]}

Ferraccioli, Gianfranco ^{[1
]}

机构：

[1] Univ Cattolica Sacro Cuore, Div Rheumatol, Fdn Policlin Univ A Gemelli, I-00168 Rome, Italy

[2] Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland

[3] Univ Cattolica Sacro Cuore, Div Pathol, Fdn Policlin Univ A Gemelli, I-00168 Rome, Italy

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

关键词：

CLASSIFICATION CRITERIA; ACTIVATION; EXPRESSION; ANTIBODY; RECEPTOR; NAIVE; DIFFERENTIATION; REGULATOR;

D O I：

10.1038/ncomms12970

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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-alpha, 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.

引用

页数：12

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