Influence Of Human Systemic Lupus Erythematosus Serum And Its IL-10 In The Developing Of Monocyte-Derived-Dendritic Cells

As the regulatory cells of immune response, dendritic cells( DC ) is attracting more and more attention in the field of autoimmune diseases. From the research results of the past decade, DC may take part in the outbreak of systemic lupus erythematosus (SLE). Some reported that SLE sera could induce the normal monocytes to develop into DC by the way of IFN-a relied, and these DCs could activate T cells. Therefore, some speculated that some cytokines in the SLE sera environment may play key roles in the disease besides those genetic factors. One hypothesis regarded that some viruses infection or others initiated the pathology process, which first induced the plasmacytoid dendritic cells(PDC) to produce IFN-a, then IFN-a induced monocytes to develop into myeloid dendritic cells(MDCs), MDCs presented self-antigen to activate self-reaction T cells and self-reaction B cells later , which secreted a lot of self-reacted antibody. If we could found the key cytokines in the process, by blocking their roles, we could have more measures in dealing with such diseases. However, the research about the abnormal development of DC and the main participators in SLE were far from known. So, at first, we established the transendothelial trafficking modelaccording to the fact that monocytes move from tissue to lymph nodes and develop into DC during the process, then we seeded peripheral blood mononuclear cells(PBMCs) in the model. By the nature of moving and trafficking, only monocytes could move into the single layer of endothelial cells and move out several days later with DCs' characters. This model followed the action of monocytes that they did in vivo. Human SLE sera and normal sera were exerted separately to investigate whether there were some abnormalities in the produced DC . Results showed that the expressive level of CD80 on SLE sera cultured MDDCs was obviously lower than that of the normal human serum, while both expressed the high level of CD86, CD11c and HLA-DR without remarkable differences. SLE sera cultured group could induce self T cells to proliferate more stronger than normal sera cultured group, which suggested that these DCs could induce more vigorous self T cells proliferation .Then we used anti IL-10 antibody to block the function of IL-10 in the SLE sera. Results showed that congenetic mixed leukocyte reaction (MLR) in SLE serum cultured group could further increase, which proved that IL-10 in SLE sera could suppress the reaction. Lastly, ELISA was done to evaluate the expression of IFN-y secreated by the cultured DCs generated from our model, and the level of IFN-y in SLE sera group was remarkablely improved compared to the nomal sera group. According to these results, we drawed the conclusion that SLE serainduced DCs existed abnormalities in development and functions.