Targeting CD226/DNAX accessory molecule-1 (DNAM-1) in collagen-induced arthritis mouse models

Muriel Elhai, Gilles Chiocchia, Carmen Marchiol, Franck Lager, Gilles Renault, Marco Colonna, Guenter Bernhardt, Yannick Allanore, Jérôme Avouac

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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. Conclusion: 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.

Original languageEnglish
Article number056
JournalJournal of Inflammation (United Kingdom)
Volume12
Issue number1
DOIs
StatePublished - 2015

Keywords

  • Autoimmunity
  • CD226
  • Collagen-induced arthritis
  • Mouse model
  • Rheumatoid arthritis

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    Elhai, M., Chiocchia, G., Marchiol, C., Lager, F., Renault, G., Colonna, M., Bernhardt, G., Allanore, Y., & Avouac, J. (2015). Targeting CD226/DNAX accessory molecule-1 (DNAM-1) in collagen-induced arthritis mouse models. Journal of Inflammation (United Kingdom), 12(1), [056]. https://doi.org/10.1186/s12950-015-0056-5