Research
Age-related changes in arthritis susceptibility and severity in a murine model of rheumatoid arthritis
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* Corresponding author: Tibor T Glant tglant@rush.edu
- † Equal contributors
1 Section of Molecular Medicine, Departments of Orthopedic Surgery, Biochemistry and Internal Medicine (Rheumatology), Rush University Medical Center, Chicago, Illinois 60612, USA
2 Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, 7643, Hungary
Immunity & Ageing 2009, 6:8 doi:10.1186/1742-4933-6-8
Published: 11 June 2009Abstract
Background
Rheumatoid arthritis (RA) most often begins in females in the fourth-fifth decade of their life, suggesting that the aging of the immune system (immunosenescence) has a major role in this disease. Therefore, in the present study, we sought to investigate the effect of age on arthritis susceptibility in BALB/c mice using the proteoglycan (PG)-induced arthritis (PGIA) model of RA.
Results
We have found that young, 1-month-old female BALB/c mice are resistant to the induction of PGIA, but with aging they become susceptible. PG-induced T cell responses decline with age, whereas there is a shift toward Th1 cytokines. An age-dependent decrease in T cell number is associated with an increased ratio of the memory phenotype, and lower CD28 expression. Antigen-presenting cells shifted from macrophages and myeloid dendritic cells in young mice toward B cells in older mice. The regulatory/activated T cell ratio decreases in older mice after PG injections indicating impaired regulation of the immune response.
Conclusion
We conclude that immunosenescence could alter arthritis susceptibility in a very complex manner including both adaptive and innate immunities, and it cannot be determined by a single trait. Cumulative alterations in immunoregulatory functions closely resemble human disease, which makes this systemic autoimmune arthritis model of RA even more valuable.