High-throughput siRNA Screen in Dendritic Cells to Discover New Genes Regulating Immunologic Tolerance

The outcome of autoantigen recognition by the immune system--self-tolerance or autoimmune disease--is largely determined by the activation state of the dendritic cells (DCs) that uptake, process, and present autoantigens to autoreactive T cells. In particular, activation of dendritic cells to an immunogenic phenotype is necessary for the full activation of naïve autoreactive T cells, and thus necessary for the initiation of autoimmune disease. A better understanding of the cellular and molecular triggers and mechanisms of DC activation could catalyze the development of novel therapies to induce self-tolerance in patients with autoimmune disease. Towards the goal of discovering new genes and pathways that regulate DC activation and immunologic self-tolerance, we (1) developed a high-throughput siRNA screen in bone marrow-derived DCs and (2) show that BMDC expression of CD80, CD86, MHC II, and IL-12/23-p40 can identify candidate genes that regulate DC activation.M.Sc.2018-03-01 00:00:0