Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice
Version of Record online: 27 APR 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 5, pages 1281–1288, May 2011
How to Cite
Blüml, S., Bonelli, M., Niederreiter, B., Puchner, A., Mayr, G., Hayer, S., Koenders, M. I., van den Berg, W. B., Smolen, J. and Redlich, K. (2011), Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis & Rheumatism, 63: 1281–1288. doi: 10.1002/art.30281
- Issue online: 27 APR 2011
- Version of Record online: 27 APR 2011
- Accepted manuscript online: 14 FEB 2011 12:15PM EST
- Manuscript Accepted: 27 JAN 2011
- Manuscript Received: 20 OCT 2010
- European Union Sixth Framework Programme. Grant Number: LSHB-CT-2006-018661
- Seventh Framework Programme. Grant Number: HEALTH-F2-2008-223404
MicroRNAs (miRNA) are a new class of regulatory elements. Altered expression of miRNA has been demonstrated in the inflamed joints of patients with rheumatoid arthritis (RA). The aim of this study was to examine the role of miRNA in the pathogenesis of autoimmune arthritis, using 2 murine models.
Collagen-induced arthritis (CIA) and K/BxN serum-transfer arthritis were induced in wild-type (WT) and miR-155–deficient (miR-155−/−) mice. The severity of arthritis was determined clinically and histologically. Anticollagen antibodies and cytokines were measured by enzyme-linked immunosorbent assay. The cellular composition of the draining lymph nodes after induction of CIA was measured by flow cytometry.
The miR-155−/− mice did not develop CIA. Deficiency in miR-155 prevented the generation of pathogenic autoreactive B and T cells, since anticollagen antibodies and the expression levels of antigen-specific T cells were strongly reduced in miR-155−/− mice. Moreover, Th17 polarization of miR-155−/− mouse T cells was impaired, as shown by a significant decrease in the levels of interleukin-17 (IL-17) and IL-22. In the K/BxN serum-transfer arthritis model, which only depends on innate effector mechanisms, miR-155−/− mice showed significantly reduced local bone destruction, attributed to reduced generation of osteoclasts, although the severity of joint inflammation was similar to that in WT mice.
These results demonstrate that miR-155 is essentially involved in the adaptive and innate immune reactions leading to autoimmune arthritis, and therefore miR-155 might provide a novel target for the treatment of patients with RA.