Targeting CD226/DNAX accessory molecule-1 (DNAM-1) in collagen-induced arthritis mouse models
Muriel Elhai1, Gilles Chiocchia2, Carmen Marchiol3
1Rheumatology 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.
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.
Insights
This study investigated the role of DNAM-1 in rheumatoid arthritis using a mouse model. Results showed that CD226/DNAM-1 does not contribute to the development of arthritis.
Area of Science:
- Immunology
- Rheumatology
- Genetics
Background:
- Genetic studies suggest CD226 variants, encoding DNAM-1, are linked to rheumatoid arthritis susceptibility.
- The role of DNAM-1 in arthritis development requires further investigation.
Purpose of the Study:
- To determine the influence of DNAM-1 on arthritis development using a collagen-induced arthritis (CIA) mouse model.
- To assess the impact of DNAM-1 deficiency and blockade on arthritis pathogenesis.
Main Methods:
- Collagen-induced arthritis (CIA) was induced in DBA/1 mice treated with anti-DNAM-1 antibody or control.
- CIA was also induced in DNAM-1 deficient (dnam1-/-) and wild-type (dnam1+/+) mice on a C57/BL6 background.
- Mice were monitored for clinical, ultrasound, and histological signs of arthritis.
Main Results:
- A non-significant trend towards a less arthritic phenotype was observed in mice treated with anti-DNAM-1 antibody.
- No significant difference in arthritis incidence or severity was found between dnam1-/- and dnam1+/+ mice.
- Histological analysis showed similar inflammatory scores and no erosions in both groups.
Conclusions:
- Complementary approaches demonstrate no contribution of CD226/DNAM-1 to the arthritic phenotype in this CIA model.
- These findings contrast with previous studies suggesting a role for DNAM-1 in other autoimmune disorders.
- The study indicates CD226/DNAM-1 is not a significant factor in rheumatoid arthritis pathogenesis.
