Novel role of plasmacytoid dendritic cells in humans: Induction of interleukin‐10–producing treg cells by plasmacytoid dendritic cells in patients with rheumatoid arthritis responding to therapy

From Vanilla to 28 Flavors: Multiple Varieties of T Regulatory Cells

A New Population of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma Patients Induces CD4+CD25+Foxp3+ T Cells

Dendritic cells are potent antigen-presenting and immune modulating cells that have been implicated in the development of atherosclerosis. In human blood, two distinct lineages are distinguished: plasmacytoid dendritic cells and myeloid dendritic cells. Although dendritic cells have been described in atherosclerotic plaques, no information exists concerning circulating blood dendritic cells in atherosclerosis. This study aims to evaluate the number of circulating dendritic cells in patients with coronary artery disease. The relation with the extent of coronary artery disease, the clinical syndrome and with a marker of inflammation will be documented. Patients with angiographically proven coronary artery disease (n=18) and age and sex-matched controls (n=18) were included. Myeloid dendritic cells and plasmacytoid dendritic cells were detected with the specific blood dendritic cell antigens, blood dendritic cell antigen-1 and blood dendritic cell antigen-2, respectively. Absolute and relative numbers of circulating plasmacytoid dendritic cells were significantly lower in patients with coronary artery disease (5722+/-601/ml and 0.08+/-0.01%) than in controls (12,640+/-1289/ml and 0.21+/-0.02%). Plasmacytoid dendritic cells were more decreased in patients with troponin-positive unstable coronary syndromes than in patients with low troponin values, and tended to be lower in more extensive coronary artery disease. Absolute myeloid dendritic cells numbers tended to be reduced in patients, whereas relative numbers were significantly decreased: 11,857+/-1895/ml versus 15,226+/-928/ml and 0.17+/-0.03% versus 0.26+/-0.01% in controls. The present study shows a significant decrease of circulating blood dendritic cell antigen-2 positive plasmacytoid dendritic cells in patients with coronary artery disease. The decrease tended to be more pronounced in unstable coronary syndromes and extensive coronary artery disease, suggesting a possible role of dendritic cells in plaque progression and rupture.

Characteristics of myeloid and plasmacytoid dendritic cells from peripheral blood were studied in healthy donors and patients with rheumatoid arthritis (RA). We evaluated relative amounts of dendritic cell by their subtypes, degree of their maturity, and ability to respond to the maturation factors (toll-like receptor 4, 7 and 8 agonists). The results of in vitro experiments have shown that the patients with rheumatoid arthritis exhibited a significant reduction in numbers of plasmacytoid dendritic cells from peripheral blood. A sufficient decrease in CD83, CD80 expression on dendritic cell subtypes in RA patients was significantly less, than in healthy donors. In patients with RA, a significant increase in the number of CCR7-expressing plasmacytoid dendritic cells was shown in peripheral blood. In stimulated cultures, maturation of dendritic cells expressing maturation markers (CD83, CD80, CCR7) proved to be increased up to normal values. It should be noted that the counts of plasmacytoid dendritic cells in peripheral blood of RA patients expressing CCR7 was significantly higher than among healthy donors. Meanwhile, expression of CD83 and CD80 increased tovalues of healthy donors. Hence, we have found a significant reduction in relative counts of blood-derived myeloid and plasmacytoid dendritic cells expressing markers of mature dendritic cells (CD83, CD80) in patients with rheumatoid arthritis. Upon stimulated in vitro maturation, the counts of myeloid and plasmacytoid dendritic cells expressing CD83 and CD80 increased to the values corresponding to those of control group. RA patients showed significantly higher numbers of plasmacytoid dendritic cells expressing CCR7. This could indicate some changes in functional activity of dendritic cells in peripheral blood of patients with RA.

The role of dendritic cells in asthma

Inhibitory oligodeoxynucleotides downregulate herpes simplex virus-induced plasmacytoid dendritic cell type I interferon production and modulate cell function

AB0023 DENDRITIC CELLS AS A PROMINENT MARKERS OF AUTOIMMUNE DISEASES

Maturation and cytokine production potential of dendritic cells isolated from rheumatoid arthritis patients peripheral blood and induced in vitro

Interactions between innate and adaptive immunity in asthma pathogenesis: New perspectives from studies on acute exacerbations

Significantly Reduced Circulating Plasmacytoid Dendritic Cells In Patients with Primary and Helicobacter Pylori-Associated Immune Thrombocytopenia

Thymic stromal lymphopoietin and allergic disease

AB0123 Microrna-mediated regulations in plasmacytoid dendritic cells in lupus mice

Hepatitis C virus infection: A “liaison a trois” amongst the virus, the host, and chronic low-level inflammation for human survival

Stimulator of Interferon Genes (STING) is a cytosolic sensor of cyclic dinucleotides (CDNs). The activation of dendritic cells (DC) via the STING pathway, and their subsequent production of type I interferon (IFN) is considered central to eradicating tumours in mouse models. However, this contribution of STING in preclinical murine studies has not translated into positive outcomes of STING agonists in phase I & II clinical trials. We therefore questioned whether a difference in human DC responses could be critical to the lack of STING agonist efficacy in human settings. This study sought to directly compare mouse and human plasmacytoid DCs and conventional DC subset responses upon STING activation. We found all mouse and human DC subsets were potently activated by STING stimulation. As expected, Type I IFNs were produced by both mouse and human plasmacytoid DCs. However, mouse and human plasmacytoid and conventional DCs all produced type III IFNs (i.e., IFN-λs) in response to STING activation. Of particular interest, all human DCs produced large amounts of IFN-λ1, not expressed in the mouse genome. Furthermore, we also found differential cell death responses upon STING activation, observing rapid ablation of mouse, but not human, plasmacytoid DCs. STING-induced cell death in murine plasmacytoid DCs occurred in a cell-intrinsic manner and involved intrinsic apoptosis. These data highlight discordance between STING IFN and cell death responses in mouse and human DCs and caution against extrapolating STING-mediated events in mouse models to equivalent human outcomes.

Plasmacytoid Dendritic Cells: A New Cutaneous Dendritic Cell Subset with Distinct Role in Inflammatory Skin Diseases