Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Micro RNA 155 Deficiency Protects from the Development of Inflammatory Arthritis.

Bluml1,  Stephan, Bonelli2,  Michael, Niederreiter1,  Birgit, Puchner1,  Antonia, Mayr1,  Georg, Koenders3,  Marije, Josef1,  Smolen

Medical University Vienna, Austria
Medical University Vienna, Austria
Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

Objective:

Micro RNAs are a new class of regulatory elements in various biological processes. Altered expression of certain micro RNAs has been demonstrated in rheumatoid arthritis. However, the pathogenic role of micro RNAs is not known in the development of this disease. The aim of this study was to assess the role of microRNA 155 in the development of murine inflammatory arthritis.

Methods:

Collagen-induced arthritis (CIA) as well as K/BxN serum transfer arthritis was in induced in wild-type (wt) and microRNA 155 knock out (miR155-/-) mice. Clinical scoring was performed on a weekly basis. Histological analysis of synovial inflammation as well as local bone destruction was performed. Cytokine production was measured in serum as well as from supernatants of cultured lymph node cells after immunization after induction of CIA. The humoral as well as T cell response to collagen as well as T cell polarization was assessed in serum, spleen and lymph node, respectively. The cellular composition of the draining LN in CIA was analyzed by flow cytometry.

Results:

We show that mice miR155-/- mice are protected from clinical as well as histological signs of CIA. Analysis of anti-collagen antibodies revealed strongly reduced levels in miR155-/- mice compared to wt. However, relative numbers and expression of costimulatory molecules on B cells were not different between the two groups. Furthermore miR155-/- mice showed reduced antigen-specific proliferation of T cells. In addition, T cells of miR155-/- mice produced significantly diminished levels of the Th17 cytokines IL-17 and IL-22, whereas Th1 and Th2 cytokine IL-4 and IFN-g were not different. Using K/BxN serum transfer arthritis, which is only dependent of innate effector mechanisms, we show that both wt and miR155-/- mice develop arthritis. However, miR155-/- mice showed significantly reduced local bone destruction due to reduced generation of osteoclasts.

Conclusions:

MiR155 deficiency protects from the development of CIA by inhibiting the generation of pathogenic self reactive T as well as B cell responses. Furthermore, miR155 controls the development of local bone destruction by inhibition of osteoclastogenesis. These data identify miR155 as a possible novel target in the therapy of autoimmune arthritis.

To cite this abstract, please use the following information:
Bluml, Stephan, Bonelli, Michael, Niederreiter, Birgit, Puchner, Antonia, Mayr, Georg, Koenders, Marije, et al; Micro RNA 155 Deficiency Protects from the Development of Inflammatory Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1351
DOI: 10.1002/art.29117

Abstract Supplement

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2010 ACR/ARHP