Dendritic Cells in Autoimmune Disease

Abstract Dendritic cells (DCs) are professional antigen presenting cells that, despite being rare populations, play a central role in many aspects of autoimmune disease pathogenesis. DC in both mouse and human can be generally divided into key subsets with distinct roles, but further specialization also occurs in some tissues. Through presenting self-antigens, DCs are critical both for activating the self-specific T cells that drive autoimmunity and for inducing antigen-specific T-cell tolerance that can mitigate pathogenesis. DC-mediated activation of autoreactive T cells can facilitate the initial break in tolerance, as well as later amplification of the response that ultimately leads to tissue destruction. Conversely, DCs are also needed for maintaining tolerance and may be able to be harnessed for immunotherapy; for example, targeting self-antigen along with tolerogenic signals may restore tolerance without disrupting immunity against pathogens. DCs integrate many signals that inform the immunity/tolerance balance. These signals include cytokines and chemokines from other immune cells as well as environmental signals that bind pattern recognition receptors such as Toll-like receptors. This chapter presents our current understanding of DC subsets, function, and relation to autoimmune disease pathogenesis and treatment.