Exacerbation of collagen type II-induced arthritis in ApoE deficient mice in association with the expansion of Th1 and Th17 cells

Objective. To explore the bidirectional relationship between the development of rheumatoid arthritis and atherosclerosis using bovine collagen type II (col II) immunized B10.RIII.ApoE mice, a murine model of spontaneous atherosclerosis and collagen-induced arthritis (CIA). Methods. B10.RIII.ApoE male mice and wild type controls were immunized with 150 g of col II emulsified in complete Freund’s adjuvant (CFA). The clinical, radiological and histopathological severity of CIA, the levels of circulating IgG1 and IgG2a anti-col II antibodies, the expression of proand anti-inflammatory cytokines in the joints and the percentages of Th1, Th17 and Treg lymphocytes in the draining lymph nodes were evaluated during CIA induction. In addition, the size of atherosclerotic lesions was assessed in these mice 8 weeks after CIA induction. Results. Col II-CFA immunized B10.RIII.ApoE mice developed an exacerbated CIA that was accompanied by increased joint expression of multiple pro-inflammatory cytokines and by the expansion in the draining lymph nodes of Th1 and Th17 cells. In contrast, the size of vascular lesions in B10.RIII.ApoE mice was not affected by the development of CIA. Conclusions. We demonstrate here that the deficiency in ApoE and/or its consequences in cholesterol metabolism act as accelerating factors in autoimmunity by promoting Th1 and Th17 inflammatory responses.