Interferon-α in the generation of monocyte-derived dendritic cells: recent advances and implications for dermatology.

ABSTRACT

Dendritic cells (DCs) have a critical role in antiviral responses, in autoimmune disease pathogenesis and in initiating and maintaining inflammatory skin disorders, and are candidates for cell-based immunotherapeutic approaches for tumours. Recent studies have shown the important role of type I interferons (IFNs) in DC differentiation and activation. In the presence of IFN-α and granulocyte/macrophage colony-stimulating factor monocytes differentiate into DCs referred to as IFN-DCs. In vitro generated IFN-DCs show a partially mature phenotype, are effective in taking up antigens, share features of myeloid DCs, plasmacytoid DCs and natural killer cells, exhibit an enhanced chemotactic response and are capable of migrating to the lymph nodes. IFN-DCs produce several chemokines and cytokines, including T-helper 1 (Th1) mediators belonging to the interleukin-12 family. IFN-DCs stimulate T- and B-cell responses and the production of IFN-γ in mixed lymphocyte reactions and have a capacity to produce IFN-γ themselves. IFN-DCs express several toll-like receptor (TLR) subtypes and TLR ligand stimulation improves their costimulatory molecule expression, increases their Th1 cytokine production and enhances their capacity to stimulate naive T-cell proliferation. Here we review the interaction of IFN-α and monocytes and the role of IFN-DCs in infections, in autoimmunity, in inflammation and in cancer immunotherapy focusing on dermatological conditions.