Functions of TGF-beta-Exposed Plasmacytoid Dendritic Cells

Plasmacytoid dendritic cells (pDCs) belong to the family of dendritic cells and possess specific features that distinguish them from conventional dendritic cells. For instance, pDC are the main interferon-alpha-secreting cells. Plasmacytoid dendritic cells exert both proinflammatory and regulatory functions. This is attested by the involvement of pDC through interferon-alpha secretion in several autoimmune diseases, and by the implication of pDC in tolerance. The same is true for TGF-beta that plays a dual role in inflammation. In this review, we discuss recent data on pDC and TGF-beta interactions. As with many cell types, pDCs are able to respond to TGF-beta using the classic Smad signaling pathway. In addition, pDCs are capable to secrete TGF-beta, in particular in response to TGF-beta exposure. Exposure of pDCs to TGF-beta prevents type I interferon secretion in response to TLR7/9 ligands. In contrast, the consequences of TGF-beta on the antigen-presenting cell capacities of pDC are less clear, since TGF-beta exposed pDCs may lead to both regulatory T-cell and interleuldn-17-secreting cell polarization. Here, we discuss the factors that may influence this polarization. We also discuss how pDCs exposed to TGF-beta may participate in tolerance induction and maintenance, or, on the contrary, in autoimmune diseases.