Good, bad and beautiful--the role of dendritic cells in autoimmunity

Autoimmunity results from a deficiency in tolerance establishment, i.e. a failure of the organism to eliminate or functionally neutralize auto-reactive lymphocytes. Dendritic cells (DC) are specialized migratory antigen presenting cells (APC), found as sentinels in peripheral tissues and lymphoid organs that allow the organism to mount rapid and efficient protective immune responses against pathogenic invaders. However, the antigenic spectrum presented by mature, highly immunogenic DC is not only of foreign origin, but includes self-proteins. As powerful stimulators of naïve T cells, DC are therefore a constant challenge to the organism emphasizing the need for trans-acting mechanisms that keep auto-reactive T cells under control. Paradoxically, recent studies indicate that DC, i.e. the same cells which represent this major threat, also play a crucial role in the establishment of both central and peripheral tolerance. In the light of a number of recent excellent reviews on the topic, this article summarizes the current knowledge obtained from the murine system highlighting hallmark experiments and open questions.