A Primary Study:Function Of Interleukin-6in Activated Lymphocyte-derived DNA(ALD-DNA) Induced Murine Systemic Lupus Erythematosus Model

Systemic lupus erythematosus (SLE) is a systematic autoimmune disease characterized by immune complex deposition, auto-antibody production and multi-organ damage. The main characteristic of the disease is the production of anti-dsDNA Abs. Anti-dsDNA Abs is found not only in the serum, but also in the kidneys of patients. The prognosis of the disease is poor, and the morbility and mortality rates of the disease have increased over the past several years. The disease can start at any age, but mainly in young women, about90%of the patients were female. SLE could not be cured now, but the symptoms can be controlled by the use of steroids and immunesuppress agents.The pathogenesis of the disease was complicated, mainly includeing the production of pathogenic auto antibodies and immune complexes, the dysfunction of T cell and NK cells, genetic and environment factors. The disease has genetic specificity, the periodicity regulation of cells, phagocytic and methylation play important roles in the pathogenesis of the disease. Most of the disease only involve one or two systems at the begining, and then cause muti-organ damage, even lupus crisis, which can be life-threatening. Because the pathogenesis of the disease is unclear, further explorations were needed in mice.Normal female C57BL/6mice were immunized with syngeneic activated lymphocyte derived DNA (ALD-DNA) to induce SLE. Non-immunized mice were used as control. SLE associated indicators, including anti-double stranded DNA Abs, urine protein, and kidney pathology was detected as indicators of the disease. The result demonstrated that comparing with control mice, ALD-DNA activated mice exhibited high levels of anti-dsDNA Abs, IL-6expression in vivo and in vitro. Results also showed that IL-6konckout (IL-6KO) mice were resiatant to ALD-DNA induced SLE. The activation of CD4+T cells in immunized IL-6KO mice was lower than in immunized Wt mice. Intracellucalr cytokine staining showed that Foxp3expression in immunized mice was higher than in immunized Wt mice. Further research demonstrate that transferring normal Treg to immunized mice could lighten the disease, while depleting CD25+cells in normal mice could result in SLE symptom.The results also indicate ALD-DNA stimulated dendritic cells supernatants could result in higher IL-6and TNF-oc expression and could suppress Foxp3expression. In addition, blocking IL-6could up-regulate Foxp3expression. Therefore, our findings show that in ALD-DNA induced SLE model, IL-6promotes the progression of the disease via suppressing Treg differention.