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Tarjanyi, O. et al.

Oktavia Tarjanyi, Ferenc Boldizsar, Peter Nemeth, Katalin Mikecz, Tibor T. Glant,

Age-related changes in arthritis susceptibility and severity in a murine model of rheumatoid arthritis.

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.[1]

References

Age-related changes in arthritis susceptibility and severity in a murine model of rheumatoid arthritis. Tarjanyi, O., Boldizsar, F., Nemeth, P., Mikecz, K., Glant, T.T. Immun. Ageing (2009) [Pubmed]

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