Dendritic cells: A doubleedge sword in autoimmune responses

Abstract

Dendritic cells (DC) are antigenpresenting cells that play a pivotal role in regulating innate and adaptive immune responses. In autoimmunity, DC act as a doubleedged sword since on one hand they initiate adaptive selfreactive responses and on the other they play a pivotal role in promoting and maintaining tolerance. Thus, DC are the most important cells in either triggering selfspecific responses or in negatively regulating autoreactive responses.The latter function is mediated by DC in the steadystate or specialized subsets of DC, named tolerogenic DC. Clinical and experimental evidence indicate that prolonged presentation of selfantigens by DC is crucial for the development of destructive autoimmune diseases, and defects in tolerogenic DC functions contribute to eradication of selftolerance. In recent years, DC have emerged as therapeutic targets for limiting their immunogenicity against selfantigens, while tolerogenic DC have been conceived as therapeutic tools to restore tolerance.The purpose of this review is to give a general overview of the current knowledge on the pathogenic role of DC in patients affected by autoimmune diseases. In addition, the protective role of tolerogenic DC will be addressed.The currently applied strategies to block immune activation or to exploit the tolerogenic potential of DC will be discussed.