title: Targeting CD226/DNAX accessory molecule-1 (DNAM-1) in collagen-induced arthritis mouse models.
abstract: BACKGROUND
  Genetic studies have pointed out that CD226 variants, encoding DNAM-1, could be associated with susceptibility to rheumatoid arthritis. Therefore, we aimed to determine the influence of DNAM-1 on the development of arthritis using the collagen-induced arthritis (CIA) mouse model.
  
  
  METHODS
  CIA was induced in mice on a DBA/1 background, treated in parallel with a DNAM-1 neutralizing monoclonal antibody, a control IgG and PBS, respectively. CIA was also induced in mice deficient for DNAM-1(dnam1-/-) and control dnam-1+/+ mice on a C57/BL6 background. Mice were monitored for clinical and ultrasound signs of arthritis. Histological analysis was performed to search for inflammatory infiltrates and erosions. The Mann-Whitney U test for non-related samples was used for statistical analysis.
  
  
  RESULTS
  There was a non-significant trend for a less arthritic phenotype in mice receiving anti-DNAM-1 mAb at both clinical, ultrasound and histological assessments. But, we did not observe any difference between dnam1+/+ and dnam1-/- mice for incidence nor severity of clinical arthritis. Histological analysis revealed inflammatory scores similar in both groups, without evidence of erosion. Collagen antibodies levels were similar in all mice, confirming immunization with collagen.
  
  
  CONCLUSIONS
  Despite some clues suggesting a role of DNAM-1 in arthritis, these complementary approaches demonstrate no contribution of CD226/DNAM-1 in the arthritic phenotype. These results contrast with previous studies showing a role in vivo of DNAM-1 in some autoimmune disorders.
authors: Rheumatology A department, Cochin Hospital, Paris Descartes University, Sorbonne Paris Cité, 27 rue du Faubourg Saint Jacques, 75014 Paris, France ; Cochin Institut, INSERM U1016, UMR 8104, Team ATIP/AVENIR, Paris Descartes University, Paris, France.
authors: Muriel
authors: M
authors: Elhai
authors: Inserm U987, Université Versailles-Saint-Quentin, Montigny-Le-Bretonneux, France.
authors: Gilles
authors: G
authors: Chiocchia
authors: Small Animal Imaging Facility, Paris Descartes University, INSERM U1016, Institut Cochin, Sorbonne Paris Cité, Paris, France.
authors: Carmen
authors: C
authors: Marchiol
authors: Small Animal Imaging Facility, Paris Descartes University, INSERM U1016, Institut Cochin, Sorbonne Paris Cité, Paris, France.
authors: Franck
authors: F
authors: Lager
authors: Small Animal Imaging Facility, Paris Descartes University, INSERM U1016, Institut Cochin, Sorbonne Paris Cité, Paris, France.
authors: Gilles
authors: G
authors: Renault
authors: Department of Pathology and Immunology, Washington University School of Medicine, St Louis, USA.
authors: Marco
authors: M
authors: Colonna
authors: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors: Guenter
authors: G
authors: Bernhardt
authors: Rheumatology A department, Cochin Hospital, Paris Descartes University, Sorbonne Paris Cité, 27 rue du Faubourg Saint Jacques, 75014 Paris, France ; Cochin Institut, INSERM U1016, UMR 8104, Team ATIP/AVENIR, Paris Descartes University, Paris, France.
authors: Yannick
authors: Y
authors: Allanore
authors: Rheumatology A department, Cochin Hospital, Paris Descartes University, Sorbonne Paris Cité, 27 rue du Faubourg Saint Jacques, 75014 Paris, France ; Cochin Institut, INSERM U1016, UMR 8104, Team ATIP/AVENIR, Paris Descartes University, Paris, France.
authors: Jérôme
authors: J
authors: Avouac
keywords: Autoimmunity; CD226; Collagen-induced arthritis; Mouse model; Rheumatoid arthritis