Dendritic cells as targets or therapeutics in rheumatic autoimmune disease

Abstract

Antigen-specific immunotherapy is a major goal for improvement in the treatment of autoimmune rheumatic disease. Dendritic cells are professional antigen-presenting cells, abundant at mucosal surfaces and in tissues. They also play a critical role in self-tolerance. This review covers recent advances in the field of dendritic cells as targets or therapeutics in rheumatic autoimmune disease. Key themes include the phenotypic and functional characterization, lineage relationships and transcription factors involved in the development of the various dendritic cell subsets. Phenotype and function of mouse and human subsets has now been much better mapped. Progress in the elucidation of targeting ligands and routes for induction of antigen-specific tolerance using either antigen-antibody fusion constructs or particulate conjugates is described. Various inflammatory molecules made by dendritic cells, including type I interferon, are important therapeutic targets in autoimmune rheumatic diseases. Approaches to block this and clinical trials in this area are discussed. There are considerable basic science developments in the field of dendritic cells and tolerance that will speed translation to human of the large amount of knowledge generated in mouse in-vivo systems. Various antigen-specific therapy approaches are in the process of translation to the clinic.