Function and dysfunction of dendritic cells in autoimmune rheumatic diseases

Dendritic cells (DC) have been implicated both in initiation of immunity and in immune tolerance. The mechanisms whereby tolerogenic DC may induce and maintain peripheral tolerance include the generation or expansion of regulatory T cells (Treg) and the promotion of T-cell anergy or deletion. A wide spectrum of hematopoietic growth factors and cytokines are endowed with the ability to differentiate tolerogenic DC both in vitro and in vivo. Based on this knowledge, therapeutic vaccination with cytokine-modulated tolerogenic DC has been applied to animal models of autoimmune disorders. This article will review the current experimental evidence underpinning DC dysfunction in rheumatic autoimmune diseases and will discuss how the manipulation of DC and Treg number and function may control undesired T-cell responses.