FRI0292 Dysfunction of Tfh, Treg and Tr1 Cells in Apoe-/- Faslgld C57bl/6 Mice with Lupus Symptoms and Atherosclerosis

Background Cardiovascular disease due to atherosclerosis is currently recognised as one of the leading causes of death among patients with systemic lupus erythematosus (SLE). It is well established that dysfunction of lymphocytes contribute to the pathogenesis of SLE. Recent studies also showed infiltration of several subsets of lymphocytes in atherosclerotic lesions and their various contributions to atherosclerosis were uncovered in experimental models and patients. However, the predominant and specific subsets of lymphocytes that play critical role in the pathogenesis of SLE patients with cardiovascular complications remained to be elucidated. Objectives This study aims to define the dominant population of lymphocytes in mice with combination of lupus and atherosclerosis. Methods The mouse model of accelerated atherosclerosis in lupus (ApoE-/- Faslgld B6 mice) was generated from apolipoprotein E-deficient (apoE-/-) and Faslgld C57BL/6 mice. The lupus-like autoimmunity and atherosclerotic lesions was evaluated. The lymphocytes of spleen and peripheral blood were analysed by flow cytometry. Results The results of PCR and sequencing showed that the double-mutant ApoE-/- Faslgld B6 mice were generated. Spleens from 5 month-old ApoE-/- Faslgld B6 mice were significantly enlarged compared with wild type mice (WT mice). ApoE-/- Faslgld B6 mice displayed a pattern of glomerulonephritis typically found in SLE and showed marked C3, IgG and IgM deposits in the glomeruli. Anti-dsDNA antibody and high levels of creatinine were detected in the serum of ApoE-/- Faslgld B6 mice. These results indicated that the ApoE-/- Faslgld B6 mice have typical characteristics of SLE. Oil red O staining revealed that there was significantly increased atherosclerotic lesion area at the proximal aorta in ApoE-/- Faslgld B6 mice compared with WT mice (figure 1 a,b). The frozen section of myocardium stained by oil red O revealed that lipid deposited in myocardial cells of ApoE-/- Faslgld B6 mice (figure 1 c,d). As excepted, total cholesterol, LDL cholesterol and triglyceride were significantly increased, while HDL cholesterol decreased in the double-mutant mice. These results indicated that ApoE-/- Faslgld B6 mice had accelerated atherosclerosis. Conclusions The ApoE-/- Faslgld B6 mice simultaneous exhibit SLE and atherosclerosis characteristics. Our findings suggested that proinflammatory M1 macrophages and Tfh cells were increased, while the anti-inflammatory Treg and Tr1 cells were decreased and the imbalance of these cells and their releasing cytokines contributed to progression in atherosclerosis with SLE. Further studies may validate these cells as potential targets for treating SLE patients with atherosclerosis. Disclosure of Interest None declared