MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27671860.
- Also identified by DOI 10.1038/ncomms12970 and PMC identifier 5052655.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-</sup>CD27<sup>-</sup> memory B-cell population in ACPA<sup>+</sup> 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.
Medical subject headings
- Arthritis, Rheumatoid
- B-Lymphocytes
- Lymphocyte Activation
- MicroRNAs
- Proto-Oncogene Proteins
- Trans-Activators