Role of dendritic cells in the pathogenesis of systemic lupus erythematosus

摘要

Given their crucial role in immunologic tolerance and immune activation, dendritic cells are considered important orchestrators of autoimmunity. Research over the past decade has revealed multiple potential mechanisms by which dendritic cells contribute to the immunopathogenesis of systemic lupus erythematosus. Genetic abnormalities in systemic lupus erythematosus can result in dendritic cells with aberrant uptake, maturation and presentation capabilities. Dysregulated apoptosis in lupus can provide a source of autoantigens for uptake by inappropriately activated dendritic cells. These cells then present autoantigen to autoreactive lymphocytes, stimulating autoantibody and immune complex formation. In addition to depositing in tissues and causing damage, these immune complexes can stimulate plasmacytoid dendritic cells via Toll-like receptors 7 and 9 to synthesize IFN-α. This cytokine exerts a host of pathogenic effects on various effector cells, including myeloid dendritic cells, generating a feedback loop that promotes a persistently and aberrantly activated immune system. Therapies that target dendritic cells may thus allow modulation of numerous immunologic abnormalities in lupus and other autoimmune diseases.