Review Article
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Role of plasmacytoid dendritic cell subsets in allergic asthma
Article first published online: 11 MAY 2013
DOI: 10.1111/all.12166
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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- Edited by: Hans-Uwe Simon
Abstract
Plasmacytoid dendritic cells (pDCs) are major type-I interferon-producing cells that play important roles in antiviral immunity and tolerance induction. These cells share a common DC progenitor with conventional DCs, and Fms-like tyrosine kinase-3 ligand is essential for their development. Several subsets of pDCs have been identified to date including CCR9+, CD9+, and CD2+ pDCs. Recently, three subsets of pDCs were described, namely CD8α−β−, CD8α+β−, and CD8α+β+ subsets. Interestingly, CD8α+β− and CD8α+β+ but not CD8α−β− pDCs were shown to have tolerogenic effects in experimentally induced allergic asthma. These tolerogenic effects were shown to be mediated by the generation of FOXP3+ regulatory T cells through retinoic acid and the induction of retinaldehyde dehydrogenase enzymes. These newly described subsets of pDCs show high potentials for novel therapeutic approaches for the treatment of allergic diseases. In this review, we will address the new progress in our understanding of pDC biology with respect to allergic disease, in particular allergic asthma.
Plasmacytoid dendritic cells (pDCs) are the major type-I interferon-producing cells that are implicated in antiviral immunity and immunological tolerance [1-6]. Since their first discovery in 1958, there has been a substantial improvement in our understanding of these cells [7]. In the steady state, pDCs show plasma cell-like morphology and express CD11c, CD45R, PDCA-1, Siglec-H, but not CD11b in mice, and CD4, CD45RA, CD303, and CD123, but not CD11c in humans [1, 8-10]. Under inflammatory conditions and upon activation, pDCs show a classical DC morphology with dendrites [11]. These cells sense pathogens through Toll-like receptor-7 and -9 leading to their rapid and robust secretion of type-I interferons (IFNs) [12, 13]. This unique capacity of pDCs to secrete high levels of IFN-α is crucial for innate antiviral immunity [14-16].
In adaptive immunity, pDCs play major roles in the induction of immunological tolerance. Unlike conventional DCs, pDCs are poor antigen-presenting cells to CD4+ T cells mainly due to their less-efficient antigen-processing machinery and low expression of co-stimulatory molecules [1, 11, 17]. However, there is evidence suggesting that pDCs can efficiently present antigens to CD8+ T cells [18]. pDCs contribute to the induction of tolerance through enhancing the generation of regulatory T (Treg) cells [19-26]. It has been shown that a subset of thymic stromal lymphopoietin protein receptor-expressing human pDCs potentiates the generation of naturally occurring T cells in the thymus [27]. There is also evidence indicating that pDCs contribute to the induction of Treg cells required for immune tolerance in allergic and autoimmune diseases, cancer, transplant and fetal tolerance [19-26].
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