Tolerogenic dendritic cells: role and therapeutic implications in systemic lupus erythematosus

Dendritic cells (DCs) are antigen presenting cells that activate T cells and determine the outcome of immune response. In addition to their important function in defense against pathogens, DCs are increasingly recognized as playing a crucial role in the regulation of immune tolerance. Plasticity of DCs with different maturity status and functions enable them to be exploited as potential cell-based therapy to restore immune tolerance in autoimmune diseases. Various ex vivo methods have been developed to generate stable tolerogenic DCs that are able to induce and maintain regulatory T cell homeostasis. The beneficial effect of tolerogenic DCs have been studied in murine autoimmune models with promising results. Systemic lupus erythematosus (SLE) is a prototypic multi-systemic autoimmune disease characterized by autoantibody production and deposition of immune complexes in organs. There are evidences that dysregulated DCs play a pivotal role in the initiation and perpetuation of lupus disease. Peripheral blood monocytes in SLE patients were found to have active phenotype with accelerated differentiation into DCs efficient in antigen presentation. Plasmacytoid DCs in SLE patients produce high levels of interferon-alpha, the signature cytokine of this disease, that cause a positive feedback loop in the amplification of activation of innate and adaptive immunity. Furthermore, manipulation of DCs via toll-like receptor knockout in a murine lupus model leads to alteration in disease severity and survival. Thus, tolerogenic DCs may appear as a potential cell-based therapeutic option in SLE.