Abstract:
BACKGROUND:The aberrant recognition of self-nucleic acids by the innate immune system contributes to the pathology of several autoimmune diseases. Although microbial DNA and, in certain instances, self-DNA that is released from damaged cells are primarily recognized by Toll-like receptor 9 (TLR9), recent evidence suggests that other cytosolic sequence-nonspecific DNA sensors contribute to DNA recognition. In this study, we focused on the sensing of microbial and host DNA in type 1 diabetes (T1D) patients. METHODS:Peripheral blood mononuclear cells (PBMCs) and monocytes from pediatric patients with T1D and from healthy donors were stimulated with microbial DNA (CpG) or with self-DNA (DNA contained within neutrophil extracellular traps, NETs). The production of cytokines was measured by flow cytometry and multiplex bead assays. The internalization of microbial DNA and its colocalization with STING was detected by image cytometry. Furthermore, the involvement of the TBK1 kinase was investigated by detecting its phosphorylation with phospho-flow cytometry or by using a TBK1 inhibition assay. RESULTS:We observed a prominent proinflammatory response in T1D PBMCs, especially pDCs and monocytes, to microbial DNA in comparison to that in controls. We further confirmed that monocytes could bind and internalize DNA and respond by releasing proinflammatory cytokines in a more pronounced manner in T1D patients than those in controls. Surprisingly, this cytokine production was not affected by TLR9 blockade, suggesting the involvement of intracellular receptors in DNA recognition. We further identified TBK1 and STING as two crucial molecules in the DNA-sensing pathway that were involved in CpG-DNA sensing by T1D cells. A similar DNA-sensing pathway that was dependent on intracellular DNA sensors and the STING-TBK1 interaction was employed in response to NETs, which were used to model self-DNA. CONCLUSIONS:Here, we show that there were significant differences in DNA sensing in T1D patients compared to that in controls. We demonstrate that monocytes from T1D patients are able to sense microbial- and self-DNA, leading to proinflammatory cytokine secretion through the adaptor protein STING and the TBK1 kinase.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Zentsova I,Parackova Z,Kayserova J,Palova-Jelinkova L,Vrabcova P,Volfova N,Sumnik Z,Pruhova S,Petruzelkova L,Sediva Adoi
10.1016/j.jaut.2019.06.005subject
Has Abstractpub_date
2019-12-01 00:00:00pages
102294eissn
0896-8411issn
1095-9157pii
S0896-8411(19)30191-Xjournal_volume
105pub_type
杂志文章abstract::Intravenous immunoglobulin (IVIg) is a therapeutic preparation consisting of pools of normal, polyspecific IgG antibodies obtained from plasma of several thousand healthy individuals. In addition to its use in primary and secondary immune deficiency, IVIg is increasingly used in the therapy of a large number of autoim...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2012.05.013
更新日期:2012-09-01 00:00:00
abstract::Class II antigens of the major histocompatibility complex (MHC) have a well-defined role in restricting cellular interactions and presenting processed antigen to T cells. In addition, a fundamental role for Class II antigens in cellular activation has been suggested, following studies demonstrating that Class II antig...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(89)90133-9
更新日期:1989-06-01 00:00:00
abstract::The detection of anti-actin (AAA) by immunofluorescence is hindered by the presence of a serum factor. To better understand how it interferes with AAA detection, we tested sera from 20 patients with autoimmune hepatitis, and from 21 healthy adults, diluted 1:10 and prepared as follows: (A) diluted with PBS; (B) inacti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0540
更新日期:2001-11-01 00:00:00
abstract::The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have be...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1999.0346
更新日期:2000-02-01 00:00:00
abstract::Coronavirus disease 2019 (COVID-19) can progress to cytokine storm that is associated with organ dysfunction and death. The purpose of the present study is to determine clinical characteristics associated with 28 day in-hospital survival in patients with coronavirus disease 2019 (COVID-19) that received tocilizumab. T...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jaut.2020.102512
更新日期:2020-11-01 00:00:00
abstract::IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and a major cause of chronic kidney disease and failure. IgAN is driven by an autoimmune reaction against galactose-deficient IgA1 that results in the generation of autoantibodies and large IgG-IgA immune complexes. Immune complexes accumulate in t...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.102309
更新日期:2019-12-01 00:00:00
abstract::Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-pos...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1035
更新日期:1994-08-01 00:00:00
abstract::To investigate patterns of autoreactivity in Sjögren's syndrome, the epitope specificity of anti-La antibodies was determined using recombinant antigens bearing sequences of the amino, middle, and carboxyl portions of the La molecule. Sera from patients with primary as well as secondary Sjögren's syndrome reacted with...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(89)90161-3
更新日期:1989-08-01 00:00:00
abstract::Autoimmune thyroid diseases (AITDs), i.e., Graves' disease (GD) and Hashimoto thyroiditis (HT), are the most prevalent organ-specific autoimmune diseases, but their pathogenesis is still incompletely understood. The PD-1/PD-L1 pathway is an important mechanism of peripheral tolerance that has not been investigated in ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.05.013
更新日期:2019-09-01 00:00:00
abstract::MHC-class II genes determine susceptibility in human type-1 diabetes. In their context, presentation of target antigen(s) results in autoimmunity and beta-cell destruction. An animal model, in which human beta-cell autoantigen(s) are presented to effector cells in the context of human MHC-class II diabetes-susceptibil...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2009.02.004
更新日期:2009-08-01 00:00:00
abstract::The development of autoimmune diseases is characterized by the breakdown of mechanism(s) that are responsible for maintaining immunological tolerance against self-structures in the periphery. Several aberrations of immune cells have been described so far. Most recently quantitative and/or qualitative defects of T cell...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2010.06.018
更新日期:2010-11-01 00:00:00
abstract::Immunostimulatory CpG motifs can preferentially induce Th1 immune responses and have been applied to treat Th2-dominant disease. In this study, we investigated whether a plasmid with the addition of 20 copies of an immunostimulatory CpG motif (pB-CpG20) might prevent the development of scleroderma-like syndrome in tig...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2005.01.014
更新日期:2005-05-01 00:00:00
abstract::Genetic polymorphism in MECP2/IRAK1 on chromosome Xq28 is a confirmed and replicated susceptibility locus for lupus. High linkage disequilibrium in this locus suggests that both MECP2 and IRAK1 are candidate genes for the disease. DNA methylation changes in lupus T cells play a central role in the pathogenesis of lupu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2012.12.012
更新日期:2013-03-01 00:00:00
abstract::Costimulatory molecules are cell-surface glycoproteins that can direct, modulate and fine tune immune responses. B7-2(CD86) costimulatory molecules are considered as major regulators of T cell responses, acting by appropriate interactions with the stimulatory CD28 or inhibitory CTLA-4 receptors found on T cells. Altho...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.06.006
更新日期:2010-11-01 00:00:00
abstract::Type 1 Diabetes (T1D) is an autoimmune disease characterized by the pancreatic infiltration of immune cells resulting in T cell-mediated destruction of the insulin-producing beta cells. The successes of the Non-Obese Diabetic (NOD) mouse model have come in multiple forms including identifying key genetic and environme...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2015.08.019
更新日期:2016-01-01 00:00:00
abstract::In a prospective study to evaluate the prevalence and predictive potential of circulating cytoplasmatic islet cell antibodies (ICA) and competitive insulin autoantibodies (CIAA), we screened 406 non-diabetic first-degree relatives of patients with Type I diabetes mellitus (n = 154 for CIAA). The prevalence of ICA was ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80029-0
更新日期:1990-10-01 00:00:00
abstract::The development of humoral autoimmunity following organ transplantation is increasingly recognised, but of uncertain significance. We examine whether autoimmunity contributes independently to allograft rejection. In a MHC class II-mismatched murine model of chronic humoral rejection, we report that effector antinuclea...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.11.006
更新日期:2019-03-01 00:00:00
abstract::The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following ...
journal_title:Journal of autoimmunity
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.jaut.2020.102434
更新日期:2020-05-01 00:00:00
abstract:BACKGROUND/PURPOSE:Primary Sjögren's syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by e...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2012.05.018
更新日期:2012-09-01 00:00:00
abstract::University of California at Davis (UCD) lines 200 and 206 chickens develop a hereditary systemic scleroderma-like connective tissue disease characterized by severe lymphocytic infiltration and excessive accumulation of collagen in skin and internal organs. The immune system seems to play an important role in the devel...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1995.0057
更新日期:1995-10-01 00:00:00
abstract::In contrast to several previously published reports, we demonstrate by a variety of antibody assays that bovine serum albumin (BSA) is not antigenically cross-reactive with the 69-kDa islet cell autoantigen (ICA69). Fast protein liquid chromatography purified BSA and highly purified recombinant human ICA69 were used t...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0199
更新日期:1998-06-01 00:00:00
abstract::T cell clones reactive to beta-cell antigens prepared from different species were established in order to identify putative pathogenic T cells in human IDDM. We were able to generate T cell clones from patients, but not from controls, reactive specifically to the insulin secretory enriched fraction (ISG) of a rat insu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1995.0017
更新日期:1995-04-01 00:00:00
abstract::Nowadays there is compelling evidence for immunoregulation by T cells. Recently, we showed that so-called 'anergic' T cells are not functionally inert but can act as regulatory cells by actively suppressing other T cell responses. We now show that 'anergic' T cells mediate this suppressive effect via modulation of the...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2000.0372
更新日期:2000-06-01 00:00:00
abstract::Physiologically, HLA Class II molecules are primarily expressed on immunoregulatory cells. In recent years, it has been shown that tissues affected by autoimmunity, including beta cells of 'diabetic' pancreases, 'inappropriately' express these glycoproteins. Cytokines are potent Class II inducers on a variety of cells...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(89)90127-3
更新日期:1989-06-01 00:00:00
abstract::The related tyrosine phosphatase-like proteins (PTP) IA-2 and IA-2beta are autoantigens of type 1 diabetes. Autoantibodies are predominantly against IA-2. We utilized the close homology between IA-2 and IA-2beta PTP domains to design chimeras and mutants in order to identify humoral IA-2-specific epitopes. Fifteen ser...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2003.08.002
更新日期:2003-12-01 00:00:00
abstract::Among B/W-derived IgM mAb, 12.5H was selected because of its ability to recognize, in solid phase ELISAs, IgG mAb with DNA-binding activity. mAb 12.5H bound preferentially to IgG2a mAb and did not react with B/W- or BALB/c-derived IgG2a mAb with no DNA-binding activity, suggesting V region-mediated interactions. mAb 1...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1056
更新日期:1994-12-01 00:00:00
abstract::The majority of patients with Dermatitis Herpetiformis (DH) have a gluten-sensitive enteropathy which may be triggered by a T cell-mediated immune response to gluten. Using a proliferative assay, the responses to gluten fraction III, recall antigens and mitogens of peripheral blood mononuclear cells (PBMC) and gut T c...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(95)90008-x
更新日期:1995-08-01 00:00:00
abstract::Ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) patients. Although type I interferons (IFN) are upregulated in SLE skin after UV exposure, the mechanisms to explain increased UVB-induced inflammation remain unclear. This paper compares the role...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.06.002
更新日期:2019-09-01 00:00:00
abstract::Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to m...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2015.07.011
更新日期:2015-09-01 00:00:00
abstract::HLA-DR0401, 0403 and 0405 are associated with variable T1D susceptibilities when linked with a common HLA-DQ8 (DQA1∗0301/DQB1∗0302). It is unknown how the modest differences within the peptide binding regions of DR4 subtypes lead to distinct autoimmune risks. Since all Class II HLA molecules share the same intracellul...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.12.004
更新日期:2011-03-01 00:00:00