title: Approaches to the pharmacological modulation of plasmacytoid dendritic cells.
abstract: Human plasmacytoid dendritic cells (pDC) are crucial for the modulation of adaptive immune responses in the course of neoplastic, viral and autoimmune diseases. In several of these disorders deregulated pDC-derived interferon-α (IFN-α), a key cytokine produced by pDC, plays a central role. Apart from IFN-α, pDC can produce a variety of other mediators, which are involved in immunological cross-talk. The most recently discovered are the cytotoxic serine protease granzyme B (GrB) and indoleamine 2,3-dioxygenase, which have been described to be involved in the suppression of effector T cell responses. Here we review the regulation of pDC function by a variety of immunomodulatory agents, which may be developed as future candidates for the therapy of a variety of diseases. Moreover, we introduce the novel concept of enhancing immune responses after vaccination in poor responders by increasing pDC-derived IFN-α and simultaneously inhibiting pDC-derived GrB secretion. Finally we discuss potential approaches to abrogate pDC-mediated tolerance induction against tumors and viral infections.
authors.affiliation: Department of Pediatrics, University of Ulm, Ulm, Germany. dorit.fabricius@uni-ulm.de
authors.forename: Dorit
authors.initials: D
authors.lastname: Fabricius
authors.forename: Bernd
authors.initials: B
authors.lastname: Jahrsdörfer
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods / Q000639:trends; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D018836:Inflammation Mediators