Fms-like tyrosine kinase 3 ligand-dependent dendritic cells in autoimmune inflammation

Dendritic cells (DCs) are specialized in capture, processing and presentation of antigens to T cells. Depending on the type of DC and its activation state, the interaction of DCs with naive T cells can lead to different types of immune response, or to T-cell tolerance. The existence of many specialized subtypes of DCs with particular functions has raised the need to distinguish DCs formed in steady-state from those produced during an inflammatory response. In patients with autoimmune disease and in experimental animal models of autoimmunity, DCs show abnormalities in both numbers and activation state, expressing immunogenic levels of co-stimulatory molecules and pro-inflammatory cytokines. Initial in vitro studies of cytokines in DC development revealed distinct and important roles for the receptor tyrosine kinases, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF, also called CSF1) and fms-like tyrosine kinase 3 ligand (Flt3L) in the generation of DCs. Flt3L is critical for instructing DC generation throughout different organs and regulates DC development from Flt3(+) lymphoid and myeloid-committed progenitors to DCs in vivo. The aim of this review is to provide an overview of the role of Flt3L-dependent DCs in the immunopathogenesis of autoimmunity and chronic inflammation and its potential as therapeutic targets.