title: Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: Stephan
authors.initials: S
authors.lastname: Blüml
authors.forename: Michael
authors.initials: M
authors.lastname: Bonelli
authors.forename: Birgit
authors.initials: B
authors.lastname: Niederreiter
authors.forename: Antonia
authors.initials: A
authors.lastname: Puchner
authors.forename: Georg
authors.initials: G
authors.lastname: Mayr
authors.forename: Silvia
authors.initials: S
authors.lastname: Hayer
authors.forename: Marije I
authors.initials: MI
authors.lastname: Koenders
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Josef
authors.initials: J
authors.lastname: Smolen
authors.forename: Kurt
authors.initials: K
authors.lastname: Redlich
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000097:blood; D007378:Interleukins / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D035683:MicroRNAs; D000097043:Interleukin-22