Dendritic Cell Biology in Animal Models of Arthritis

Abstract

Abstract:In recent years the treatment of rheumatoid arthritis (RA) has changed considerably with the advent of novel biologic agents that target cytokines such as TNF. The impact on clinical practice has been considerable with achievement of high hurdle endpoints and reduced articular damage. Unfortunately, remission that is long lasting is rarely achieved and almost never reached in the absence of chronic drug therapy. Thus, interest in what should be the critical objective of autoimmune therapeutics -the re-establishment of self-tolerance -has become increasingly prominent.Models of experimental arthritis have only just begun to reveal the intricacies of dendritic cell (DC) biology in RA. And while manipulation of antigen presenting cells such as DCs can be used in the suppression of experimental arthritis, the basic functions and mechanisms regarding their impact is mostly obtained indirectly by inference from other autoimmune and infectious studies. Indeed, our understanding of the contribution of DC biology to induction and perpetuation of RA is relatively ill defined. Here we discuss recent advances in understanding basic DC biology, their roles in, and impact on, experimental arthropathy and resulting therapeutic implications. It is essential that more research into the direct contribution of DC activity in RA is forthcoming, particularly as they could hold the key to development of antigen specific therapeutics. The major contributing factor to this knowledge deficit is the difficulty inherent in investigating what are most likely pre-clinical immunological events, an area more suited to study in animal models.