Carissa Rodriquez

Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs, including joints, skin, kidneys, heart, hematopoietic system, and nervous system. SLE primarily affects women, and there is an estimated 1.5 million people in the United States who are suffering from SLE. SLE is triggered in those who are genetically susceptible when they encounter environmental triggers such as UV exposure, drugs or infection¹. Nucleic acid recognition receptors, like members of the Toll-like receptor (TLR) family, are activated by persistent apoptotic debris that results from the environmental triggers. TLR-7 and TLR-9 are receptors associated with plasmacytoid dendritic cells (pDCs), which produce high amounts of type I IFNs in response to recognition of viruses or self-nucleic acids^2-4. Studies have found that when pDCs are depleted in mice during the early stages of the disease or during inflammation, there is a reduced severity in SLE^5,6. Other studies show that the serum concentration of human IgE antibodies can potentiate type I IFN responses, while tumor necrosis stimulated gene 6 (TSG-6) can downregulate it^7,8. These findings could suggest potential therapeutic targets for the treatment of SLE. Methods. Transgenic mice with the pDC promotor BDCA2 were treated with diphtheria toxin to selectively ablate pDCs and then crossed with autoimmune-prone BXSB mice. Their immune cells, antibody production, and tissue analysis were observed⁵. A nonviral inflammatory response was induced in naïve mice and their pDC levels were observed with flow cytometry⁶. The concentration of IgE in patient serum was measured with ELISA⁷. TLR7/9 activated pDCs were treated with recombinant TSG-6 to observe the response⁸. Results. When pDCs are depleted early in the disease, there was reduced activation and expansion of immune cells, limited autoantibody production, and less severe glomerulonephritis⁵. During inflammation, CD8+T cells induce apoptosis through the perforin pathway⁶. The concentration of self-reactive ds-DNA-IgE in serum correlated with disease severity⁷. TSG-6 can downregulate IFN-a⁸. Conclusions. Studies have shown the potential role plasmacytoid dendritic cells play in systemic lupus erythematous. pDCs represent a therapeutic target for the treatment of SLE. The CD8+T cell response, IgE functions, and the TSG-6 regulatory mechanisms may contribute to the treatment of SLE by decreasing and regulating pDCs in susceptible patients.

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