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.
Keywords: pDC, IFN-α, TNF-α, granzyme B, TRAIL, IDO, HMGB1, IL-6, IL-12, IP-10, Interleukin, Vasoactive intestinal peptide
Endocrine, Metabolic & Immune Disorders - Drug Targets
Title: Approaches to the Pharmacological Modulation of Plasmacytoid Dendritic Cells
Volume: 11 Issue: 2
Author(s): Dorit Fabricius and Bernd Jahrsdorfer
Affiliation:
Keywords: pDC, IFN-α, TNF-α, granzyme B, TRAIL, IDO, HMGB1, IL-6, IL-12, IP-10, Interleukin, Vasoactive intestinal peptide
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.
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Cite this article as:
Fabricius Dorit and Jahrsdorfer Bernd, Approaches to the Pharmacological Modulation of Plasmacytoid Dendritic Cells, Endocrine, Metabolic & Immune Disorders - Drug Targets 2011; 11 (2) . https://dx.doi.org/10.2174/187153011795564205
DOI https://dx.doi.org/10.2174/187153011795564205 |
Print ISSN 1871-5303 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3873 |
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