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Systemic Lupus Erythematosus
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Vaneet K. Sandhu, Neha V. Chiruvolu, Daniel J. Wallace
For many years, the understanding of SLE pathophysiology was highly focused on autoantibodies, which expectedly led to therapeutic targeting of antibody production. However, this explained only part of disease pathogenesis. In addition to the adaptive immune response, the innate immune response also plays an important role. Multiple studies have identified the role of IFN-I, particularly IFN-α, in the pathogenesis of SLE. Prior to this, IFN had been well studied in antiviral defense. Elevated IFN in sera of SLE patients was first noted in 1979. This was followed by cumulative evidence of elevated IFN-1 receptor activation in SLE. Recent research in gene signaling has supported this observation, showing activation of genes involved in IFN-1 signaling. As opposed to viral infections where IFN-1 levels are elevated only during infection, studies have shown that IFN-1 levels are chronic in SLE patients, but there is poor evidence of correlation with disease flares. Plasmacytoid dendritic cells (pDC) are the prime IFN-α-producing cells, and there is evidence of their role in inflammation in SLE. Furthermore, it seems that immune complexes with nucleic acid, specifically RNA (Ro, La, Sm, RNP), can trigger IFN production through toll-like receptor 7 (TLR7).
Probiotics as HRV Vaccine Adjuvants in Gn Pigs
Published in Lijuan Yuan, Vaccine Efficacy Evaluation, 2022
In the following section, the findings from our serial studies of Gn pigs on the dose effects of the probiotic LA on innate and adaptive immune responses induced by the oral AttHRV vaccine are discussed (Yuan et al., 2013). We studied the effects of low dose (total 2.11 × 106CFU) and high dose (total 2.22 × 109CFU) LA on the intestinal and systemic 1) rotavirus-specific IFN-γ producing CD4+ and CD8+ T cell responses; 2) CD4+CD25+FoxP3+ and CD4+CD25−FoxP3+ Treg cell responses and the regulatory cytokine TGF-β and IL-10 production; 3) rotavirus-specific ASC and serum antibody responses; and 4) plasmacytoid dendritic cell (pDC) and conventional DC (cDC) frequencies, activation status, TLR expression, and cytokine production profile. The protective effect of the rotavirus vaccine against virus shedding and diarrhea was assessed in AttHRV-vaccinated Gn pigs fed with high, low, or no LA and challenged with the VirHRV.
Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCN)
Published in Dongyou Liu, Tumors and Cancers, 2017
As highly specialized circulating cells of the innate immune system, plasmacytoid dendritic cells are capable of producing high levels of type I interferon (IFN-I) and differentiating clonally into antigen-presenting dendritic cells upon stimulation. Thus, by bridging the innate and acquired components of the immune responses, plasmacytoid dendritic cells play important roles in defense against pathogens, cancer, and autoimmunity.
Targeting citrullination in autoimmunity: insights learned from preclinical mouse models
Published in Expert Opinion on Therapeutic Targets, 2021
Ylke Bruggeman, Fernanda M.C. Sodré, Mijke Buitinga, Chantal Mathieu, Lut Overbergh, Maria J.L. Kracht
SLE is a systemic autoimmune disease that causes damage to multiple organs, including the skin, kidneys and joints. In addition, cardiovascular complications typically arise in patients with SLE as a result of accelerated atherosclerosis and represent an important morbidity cause [86]. Characteristic for SLE is the presence of autoantibodies against nuclear antigens. Accumulation of these nuclear autoantigens results from dying cells and impaired clearance of debris [87]. Deposition of immune complexes (ICs) in tissues stimulate the production of type I Interferons (IFNs) by plasmacytoid dendritic cells (pDCs), driving disease pathogenesis [88]. Many cell death pathways have been implicated as a source of nuclear autoantigens, including apoptosis, necroptosis, pyroptosis, autophagy and NETosis [87,89,90]. Neutrophils, found in kidneys and skin of lupus-patients, showed an increased capacity to release NETs [91]. Lupus NETs also induced pDCs to produce type I IFNs and directly promoted vascular and organ damage [90–92].
Dendritic cells in COVID-19 immunopathogenesis: insights for a possible role in determining disease outcome
Published in International Reviews of Immunology, 2021
Rodrigo Cerqueira Borges, Miriam Sayuri Hohmann, Sergio Marques Borghi
Dendritic cells are a diverse group of professional antigen-presenting cells (APCs) with central roles in the initiation and regulation of innate and adaptive immune responses. Dendritic cells comprise several subsets, which have distinct roles in initiating immunity to specific pathogens. There are two main categories of dendritic cells, plasmacytoid and conventional dendritic cells [44]. Plasmacytoid dendritic cells are an important source of type I IFN and, following their activation, are critical for the initial antiviral responses. Conventional dendritic cells are present in the thymus, spleen, and lymphoid nodes and can be further categorized into 2 categories depending on the paths followed to access the lymphoid organs: 1) blood-derived or resident dendritic cells, which develop from the bone marrow precursors within lymphoid organs without trafficking through peripheral tissues and 2) migratory dendritic cells, which develop from earlier precursors in peripheral tissues and, following the encounter with a pathogen, migrate to draining lymph nodes to interact with T cells and prime adaptive immunity [44, 45].
An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial
Published in OncoImmunology, 2020
Julie Charles, Laurence Chaperot, Dalil Hannani, Juliana Bruder Costa, Isabelle Templier, Sabiha Trabelsi, Hugo Gil, Anaick Moisan, Virginie Persoons, Harald Hegelhofer, Edith Schir, Jean-Louis Quesada, Christophe Mendoza, Caroline Aspord, Olivier Manches, Pierre G. Coulie, Amir Khammari, Brigitte Dreno, Marie-Thérèse Leccia, Joel Plumas
With the advent of antibodies against immune checkpoints, cancer treatment entered in a new era. However, despite the clinical benefit observed in a large series of cancer indications, few patients respond to monotherapy. Thus, to increase the proportion of patients that could benefit from ICI, many clinical trials are conducted that combine these drugs with other treatments such as chemotherapy, targeted therapy or radiotherapy.23 Since ICI efficacy has been shown to depend on the presence of preexisting antitumor T cells, its combination with antitumor vaccination represents an attractive therapeutic approach.10 Vaccination with tumor-specific antigens can prime antitumor T cells whose restimulation can then be boosted by ICI. Moreover, it ought to increase the ratio between antitumor T cells and antimicrobial or antiself T cells, decreasing the autoimmune and inflammatory side effects of ICI. Diverse vaccine platforms can be used for therapeutic vaccination including proteins/peptides, RNA or DNA, viral-vector-based, tumor cells or dendritic cells-based vaccines.24 Among dendritic cells, plasmacytoid dendritic cells are of great interest.13 In murine models, PDC that were properly loaded with tumor antigens and activated induced strong CTL responses and tumor regression.17,25