Abstract:
:Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER) stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α) signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein β-dependent trans-activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Márquez S,Fernández JJ,Terán-Cabanillas E,Herrero C,Alonso S,Azogil A,Montero O,Iwawaki T,Cubillos-Ruiz JR,Fernández N,Crespo MSdoi
10.3389/fimmu.2017.00639subject
Has Abstractpub_date
2017-06-19 00:00:00pages
639issn
1664-3224journal_volume
8pub_type
杂志文章abstract::Background: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship bet...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01948
更新日期:2018-08-28 00:00:00
abstract::Experimental evidence indicates that mesenchymal stromal cells (MSCs) may regulate tumor microenvironment (TME). It is conceivable that the interaction with MSC can influence neoplastic cell functional behavior, remodeling TME and generating a tumor cell niche that supports tissue neovascularization, tumor invasion an...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00262
更新日期:2018-02-19 00:00:00
abstract::Breast cancer is characterized by cellular and molecular heterogeneity. Several molecular events are involved in controlling malignant cell process. In this sense, the importance of studying multiple cell alterations in this pathology is overriding. A well-identified fact on immune response is that it can vary depend ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00348
更新日期:2019-03-01 00:00:00
abstract::Neuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care therapies belie the critical need for more tolerable and effective ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00873
更新日期:2020-05-08 00:00:00
abstract::The intestinal mucosa is constantly facing a high load of antigens including bacterial antigens derived from the microbiota and food. Despite this, the immune cells present in the gastrointestinal tract do not initiate a pro-inflammatory immune response. Toll-like receptors (TLRs) are pattern recognition receptors exp...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00060
更新日期:2014-02-18 00:00:00
abstract::CD27 expression has been used to distinguish between memory and naive B cells in humans. However, low levels of mutated and isotype-switched CD27-IgD- cells are seen in healthy adults, and these are increased in some autoimmune diseases and in the elderly. Thus CD27 is not a universal marker of memory B cells in human...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2011.00081
更新日期:2011-12-26 00:00:00
abstract::The study of molecular host-parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require a clear understanding of the molecular crosstalk between parasites and their hosts. Yet, large-scale experimental iden...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00212
更新日期:2019-02-13 00:00:00
abstract::T cells are the main orchestrators of protective immunity in the stomach; however, limited information on the presence and function of the gastric T subsets is available mainly due to the difficulty in recovering high numbers of viable cells from human gastric biopsies. To overcome this shortcoming we optimized a cell...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00294
更新日期:2014-06-19 00:00:00
abstract::Secondary lymphoid tissues such as lymph nodes are essential for the interactions between antigen presenting cells and lymphocytes that result in adaptive immune responses that protect the host against invading pathogens. The specialized architecture of these organs facilitates the cognate interactions between antigen...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00381
更新日期:2012-12-14 00:00:00
abstract::[This corrects the article DOI: 10.3389/fimmu.2019.00917.]. ...
journal_title:Frontiers in immunology
pub_type: 已发布勘误
doi:10.3389/fimmu.2019.01528
更新日期:2019-07-02 00:00:00
abstract::Isatuximab is a monoclonal antibody targeting the transmembrane receptor and ectoenzyme CD38, a protein highly expressed on hematological malignant cells, including those in multiple myeloma (MM). Upon binding to CD38-expressing MM cells, isatuximab is thought to induce tumor cell killing via fragment crystallizable (...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01771
更新日期:2020-08-14 00:00:00
abstract::Hemagglutinin glycoprotein (HA) is a principle influenza vaccine antigen. Recombinant HA-based vaccines become a potential alternative for traditional approach. Complexity and variation of HA N-glycosylation are considered as the important factors for the vaccine design. The number and location of glycan moieties in t...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00444
更新日期:2017-04-20 00:00:00
abstract::The neonatal Fc receptor (FcRn) plays key roles in IgG and albumin homeostasis, maternal IgG transport, and antigen presentation of IgG-opsonized antigens. Previously, we reported that transgenic (Tg) mice that overexpress the bovine FcRn (bFcRn) have augmented T-dependent humoral immune response with increased IgG pr...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2015.00357
更新日期:2015-07-20 00:00:00
abstract::Approximately 40% of preterm births are preceded by microbial invasion of the intrauterine space; ascent from the vagina being the most common pathway. Within the cervical canal, antimicrobial peptides and proteins (AMPs) are important components of the cervical barrier which help to prevent ascending vaginal infectio...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00106
更新日期:2020-02-11 00:00:00
abstract::Inflammation is a crucial defense mechanism that protects the body from the devastating effects of invading pathogens. However, an unrestrained inflammatory reaction may result in systemic manifestations with dire consequences to the host. The extent of activation of the inflammatory response is tightly regulated thro...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00551
更新日期:2018-03-19 00:00:00
abstract::Dendritic cells (DCs), Langerhans cells (LCs), and macrophages are innate immune cells that reside in genital and intestinal mucosal tissues susceptible to HIV-1 infection. These innate cells play distinct roles in initiation of HIV-1 infection and induction of anti-viral immunity. DCs are potent migratory cells that ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00059
更新日期:2012-03-26 00:00:00
abstract::Autoimmune diseases, such as systemic lupus erythematosus, are characterized by excessive inflammation in response to self-antigens. Loss of appropriate immunoregulatory mechanisms contribute to disease exacerbation. We previously showed the suppressive effect of vancomycin treatment during the "active-disease" stage ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.593353
更新日期:2020-11-10 00:00:00
abstract::Disialoganglioside GD2 is an important target on several pediatric and adult cancer types including neuroblastoma, retinoblastoma, melanoma, small-cell lung cancer, brain tumors, sarcomas, and cancer stem cells. We have utilized structural and computational methods to refine the framework of humanized monoclonal antib...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2014.00372
更新日期:2014-08-14 00:00:00
abstract::MHC class I (MHC-I) polymorphisms are associated with the outcome of some viral infections and autoimmune diseases. MHC-I proteins present antigenic peptides and are recognized by receptors on natural killer cells and cytotoxic T lymphocytes, thus enabling the immune system to detect self-antigens and eliminate target...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00281
更新日期:2016-07-25 00:00:00
abstract::Background: B-1a B cells and gut secretory IgA (SIgA) are absent in asplenic mice. Human immunoglobulin M (IgM) memory B cells, which are functionally equivalent to mouse B-1a B cells, are reduced after splenectomy. Objective: To demonstrate whether IgM memory B cells are necessary for generating IgA-secreting plasma ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02937
更新日期:2020-01-08 00:00:00
abstract::Volcanic ash is a heterogeneous mineral dust that is typically composed of a mixture of amorphous (glass) and crystalline (mineral) fragments. It commonly contains an abundance of the crystalline silica (SiO2) polymorph cristobalite. Inhalation of crystalline silica can induce inflammation by stimulating the NLRP3 inf...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.02000
更新日期:2018-01-22 00:00:00
abstract::The pathogenesis of dengue hemorrhagic fever (DHF), following dengue virus (DENV) infection, is a complex and poorly understood phenomenon. In view of the clinical need of identifying patients with higher likelihood of developing this severe outcome, we undertook a comparative genome-wide association analysis of epito...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00728
更新日期:2018-04-10 00:00:00
abstract::FcγRIIa is an activating FcγR, unique to humans and non-human primates. It induces antibody-dependent proinflammatory responses and exists predominantly as FcγRIIa1. A unique splice variant, we designated FcγRIIa3, has been reported to be associated with anaphylactic reactions to intravenous immunoglobulins (IVIg) the...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01809
更新日期:2018-08-20 00:00:00
abstract::Adult-onset primary immunodeficiency is characterized by recurrent infections, hypogammaglobulinemia, and poor antibody response to vaccines. In this study, we have analyzed targeted gene panel sequencing results of 270 patients diagnosed with antibody deficiency and identified five disease-associated variants in NFKB...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02618
更新日期:2019-11-14 00:00:00
abstract::Antibodies that block the immune checkpoint receptors PD1 and CTLA4 have revolutionized the treatment of melanoma and several other cancers, but in the process, a new class of drug side effect has emerged-immune related adverse events. The observation that therapeutic blockade of these inhibitory receptors is sufficie...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02306
更新日期:2018-10-08 00:00:00
abstract::Tolerogenic dendritic cells (DCs) work through silencing of differentiated antigen-specific T cells, activation and expansion of naturally occurring T regulatory cells (Tregs), transfer of regulatory properties to T cells, and the differentiation of naïve T cells into Tregs. Due to an operational definition based on T...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00113
更新日期:2013-05-14 00:00:00
abstract::The impact of the highly polymorphic Killer-cell immunoglobulin-like receptor (KIR) gene cluster on the outcome of hematopoietic stem cell transplantation (HCST) is subject of current research. To further understand the involvement of this gene family into Natural Killer (NK) cell-mediated graft-versus-leukemia reacti...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00429
更新日期:2020-03-12 00:00:00
abstract::Ectoenzyme and receptor BST-1/CD157 has been considered as a key molecule involved in the regulation of functional activity of cells in various tissues and organs. It is commonly accepted that CD157 catalyzes NAD+ hydrolysis and acts as a component of integrin adhesion receptor complex. Such properties are important f...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.585294
更新日期:2020-11-10 00:00:00
abstract::Liver fibrosis is the final common pathway of chronic liver diseases irrespective of etiology. However, etiology deeply impacts progression and characteristics of liver fibrogenesis. IL-13 is the dominant pro-fibrotic cytokine in Schistosomiasis associated liver fibrogenesis. In vitro, IL-13 directly induces expressio...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00116
更新日期:2012-05-11 00:00:00
abstract::Cancer stem cells (CSCs) have been identified as the source of tumor growth and disease recurrence. Eradication of CSCs is thus essential to achieve durable responses, but CSCs are resistant to current anti-tumor therapies. Novel therapeutic approaches that specifically target CSCs will, therefore, be crucial to impro...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01412
更新日期:2018-06-19 00:00:00