Abstract：
:TREX1 encodes a major cellular DNA exonuclease. Mutations of this gene in human cause cellular accumulation of DNA that triggers autoimmune diseases including Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE). We created a lupus mouse model by engineering a D18 N mutation in the Trex1 gene which inactivates the enzyme and has been found in human patients with lupus-like disorders. The Trex1D18N/D18N mice exhibited systemic inflammation that consistently recapitulates many characteristics of human AGS and SLE. Importantly, ablation of cGas gene in the Trex1D18N/D18N mice rescued the lethality and all detectable pathological phenotypes, including multi-organ inflammation, interferon stimulated gene induction, autoantibody production and aberrant T-cell activation. These results indicate that cGAS is a key mediator in the autoimmune disease associated with defective TREX1 function, providing additional insights into disease pathogenesis and guidance to the development of therapeutics for human systemic autoimmune disorders.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Xiao N,Wei J,Xu S,Du H,Huang M,Zhang S,Ye W,Sun L,Chen Qdoi
10.1016/j.jaut.2019.03.001subject
Has Abstractpub_date
2019-06-01 00:00:00pages
84-94eissn
0896-8411issn
1095-9157pii
S0896-8411(19)30035-6journal_volume
100pub_type
杂志文章abstract：:Therapy with anti-CD3 antibody is effective in controlling models of autoimmune diseases and can reverse or prevent rejection of grafts. We studied the in vitro immunomodulatory effect of anti-CD3 treated human T cells. CD4(+) T cells were stimulated with plate-bound anti-CD3 and cultured for 12 days after which they ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2007.11.007
更新日期：2008-02-01 00:00:00
abstract：:The induction and persistence of a hypo-inflammatory and immunosuppressive state in severe sepsis is commonly associated with increased risks of secondary infections and mortality. Toll-like receptor (TLR)-triggered inflammatory response of macrophages/monocytes plays an important role in determining the outcome of hy...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2017.04.006
更新日期：2017-07-01 00:00:00
abstract：:Sjögren's syndrome (SS) is a chronic autoimmune disorder that is characterized by dysfunction and destruction of the exocrine glands. Exocrinopathy is associated with periductal mononuclear cell infiltrates in the affected exocrine glands and B-cell hyperreactivity. Epithelial cells are thought to play an important pa...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2010.06.011
更新日期：2010-11-01 00:00:00
abstract：:HLA-DQB1 is widely considered to be the major histocompatibility complex (MHC) susceptibility gene for type 1 diabetes (T1D). However, since inheritance of the gene in T1D is recessive, the presence of the protective HLA-DQB1 0602 allele with normal nucleotide sequence in some patients raises the question of whether H...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2007.10.006
更新日期：2008-06-01 00:00:00
abstract：:TNF-alpha is a pleiotropic cytokine that is constitutively expressed in the thymus. This cytokine has opposing effects on type 1 diabetes mellitus (T1DM) as non-obese diabetic (NOD) mice administered TNF-alpha early in life experience an acceleration in disease onset while TNF-alpha administered to adult NOD mice are ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2007.06.002
更新日期：2007-09-01 00:00:00
abstract：:We have previously described an SLE-derived human hybridoma autoantibody, 9604, which binds to activated but not to resting platelets, inhibits platelet aggregation, and immunoprecipitates a surface-labelled poly-peptide of 32,000 molecular weight (MW) (p32). In the present study, using a murine monoclonal anti-p32 an...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1995.0008
更新日期：1995-02-01 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：:Approximately 25% of mature T cells possess two distinct cytoplasmic T cell receptor (TCR) alpha-chains, due to productive gene rearrangements of both alleles. Expression of two different alpha-chains at the cell surface is a potential risk factor for development of autoimmunity. However, it has been difficult to dete...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.2001.0504
更新日期：2001-06-01 00:00:00
abstract：:Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium with limited therapeutic options. It is a heterogeneous group of cancer that could develop at any level from the biliary tree and is currently classified into intrahepatic, perihilar and distal based on its anatomical location. With incidence and mo...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2019.03.007
更新日期：2019-06-01 00:00:00
abstract：:Since its description in 1965, Sneddon syndrome (SNS) is usually characterized by the association of an ischemic cerebrovascular disease and a widespread livedo reticularis. The presence of many other manifestations suggests that it is a systemic syndrome. The prevalence of anti-phospholipid antibodies (aPL) is highly...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1006/jaut.2000.0418
更新日期：2000-09-01 00:00:00
abstract：:Experimental autoimmune encephalomyelitis (EAE) is a model of T-cell mediated autoimmune disease. Active disease is mediated by myelin basic protein specific CD4+ T-cells, whose adoptive transfer can also induce passive disease. In the Lewis rat EAE is a transient disease inducing lasting resistance to rechallenge. Th...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1995.0031
更新日期：1995-06-01 00:00:00
abstract：:Autoinflammatory diseases (AUIDs) are a genetically heterogeneous group of rheumatic diseases characterized by episodic inflammation linked with dysregulated innate immune responses. In this review, we summarize the molecular mechanisms altered by disease-associated variants in several AUIDs, including NOD2-associated...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2017.10.012
更新日期：2018-03-01 00:00:00
abstract：:To study the potential roles of cytokines in development and resolution of granulomatous experimental autoimmune thyroiditis (EAT), the kinetics of in vivo expression of cytokine genes in thyroid infiltrates was analysed using reverse transcriptase-PCR (RT-PCR). Both Th1 (IL-2 and IFN-gamma) and Th2 (IL-4 and IL-10) c...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1998.0247
更新日期：1998-12-01 00:00:00
abstract：:Bullous pemphigoid (BP) and linear IgA disease (LAD) are autoimmune subepidermal blistering skin diseases associated with autoantibodies against the transmembrane hemidesmosomal protein BP180/type XVII collagen. It has been demonstrated previously that BP is characterized predominantly by IgG autoantibodies, while aut...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.2000.0437
更新日期：2000-11-01 00:00:00
abstract：:Allogeneic hematopoietic cell transplantation (HCT) is an increasingly widely used treatment modality in hematological malignancies. Alloreactivity mediated by donor T cells (and, in some settings, by donor natural killer cells) can produce durable immunologic control or eradication of residual malignancy after alloge...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2007.12.002
更新日期：2008-05-01 00:00:00
abstract：:Autoantigen-specific TCR transgenic mice allow us to assess the role of T cells in autoimmunity. We have recently generated humanized TAZ10 transgenic mice expressing the human TCR specific for the immunodominant epitope of thyroid peroxidase (TPO). We have shown that these transgenic mice do not undergo tolerance in ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2005.01.003
更新日期：2005-03-01 00:00:00
abstract：:Beta(2)-glycoprotein I (beta(2)GPI) is known as a major autoantigen for antiphospholipid antibodies. Our recent data show that binding of beta(2)GPI to oxidized low-density lipoprotein (oxLDL) or to liposomes containing anionic phospholipid(s) may facilitate the presentation of beta(2)GPI's epitope by macrophages/dend...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2007.07.003
更新日期：2007-09-01 00:00:00
abstract：:The mechanism by which immune tolerance is breached in autoimmune disease is poorly understood. One possibility is that post-translational modification of self-antigens leads to peripheral recognition of neo-epitopes against which central and peripheral tolerance is inadequate. Accumulating evidence points to multiple...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2017.08.001
更新日期：2017-11-01 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：: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 complement component C4 is encoded by two genes: C4A and C4B on human chromosome 6p in the major histocompatibility complex (MHC). Most studies have linked the deficiencies in C4 with systemic lupus erythematosus (SLE) in Angio-Irish, North American, Black American, Mexican American, Australian and Japanese popula...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2005.04.004
更新日期：2005-08-01 00:00:00
abstract：:The obstetric management of women with antiphospholipid (aPL) syndrome remains controversial. Despite recent advances, the controversies have been fueled by our limited understanding of the multi-factorial causes of aPL-associated pregnancy loss and the lack of data from randomized studies. We have escaped from the na...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1006/jaut.2000.0417
更新日期：2000-09-01 00:00:00
abstract：:Mesenchymal stem cells (MSCs) are considered to be a promising platform for cell and gene therapy for a variety of diseases. First, in the field of hematopoietic stem cell transplantation, there are two applications of MSCs: 1) the improvement of stem cell engrafting and the acceleration of hematopoietic reconstitutio...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2007.12.008
更新日期：2008-05-01 00:00:00
abstract：:CD8(+) cytotoxic T lymphocytes (CTL) can rapidly kill beta-cells and therefore contribute to the development of type 1 diabetes (T1D). CTL-mediated beta-cell killing can occur via perforin-mediated lysis, Fas-Fas-L interaction, and the secretion of TNF-alpha or IFN-gamma. The secretion of IFN-gamma can contribute to b...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2006.08.002
更新日期：2006-11-01 00:00:00
abstract：:The clinical manifestations of graft rejection or autoimmune disease represent the terminal phase in a complex sequence of inflammatory events. Although the spectrum of response to injury within each tissue is normally narrowly defined, the immune mechanisms involved may be heterogeneous, influenced by the immune stat...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/0896-8411(92)90052-r
更新日期：1992-04-01 00:00:00
abstract：:The effector mechanisms responsible for autoimmune beta cell destruction in insulin dependent (type 1) diabetes (IDD) remain elusive. In order to investigate whether T lymphocytes bearing the gamma-delta T cell receptor (gamma delta+ T cells) could be involved in this process, we measured percentages of peripheral blo...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(91)90055-h
更新日期：1991-12-01 00:00:00
abstract：:Polymyalgia rheumatica is the most common inflammatory rheumatic disease of the elderly, and shares many pathogenetic and epidemiological features with giant cell arteritis. The typical symptoms are bilateral aching of the shoulder girdle, associated with morning stiffness. The neck and hip girdle may also be involved...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2014.01.016
更新日期：2014-02-01 00:00:00
abstract：:Wegener's autoantigen (WA), a 29 kD multifunctional protein, is the principal target antigen of autoantibodies associated with Wegener's granulomatosis (WG). WA was first identified as proteinase 3 (PR3), which is now known to be identical with myeloblastin and AGP7. Like other lysosomal proteins, WA/PR3 displays enzy...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1006/jaut.1993.1015
更新日期：1993-04-01 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 72 kD heat shock protein (hsp 72) has been postulated to play a role in the development of autoimmune disease and has been shown to be overexpressed in the Graves' disease thyroid gland. The expression and modulation of the 72 kD heat shock protein were therefore studied in cultured human thyroid epithelial cells ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1994.1017
更新日期：1994-04-01 00:00:00
