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 environmental risk factors e.g. Idd loci and effects of microorganisms including the gut microbiota, respectively, and how they may contribute to disease susceptibility and pathogenesis. Furthermore, the NOD model also provides insights into the roles of the innate immune cells as well as the B cells in contributing to the T cell-mediated disease. Unlike many autoimmune disease models, the NOD mouse develops spontaneous disease and has many similarities to human T1D. Through exploiting these similarities many targets have been identified for immune-intervention strategies. Although many of these immunotherapies did not have a significant impact on human T1D, they have been shown to be effective in the NOD mouse in early stage disease, which is not equivalent to trials in newly-diagnosed patients with diabetes. However, the continued development of humanized NOD mice would enable further clinical developments, bringing T1D research to a new translational level. Therefore, it is the aim of this review to discuss the importance of the NOD model in identifying the roles of the innate immune system and the interaction with the gut microbiota in modifying diabetes susceptibility. In addition, the role of the B cells will also be discussed with new insights gained through B cell depletion experiments and the impact on translational developments. Finally, this review will also discuss the future of the NOD mouse and the development of humanized NOD mice, providing novel insights into human T1D.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Pearson JA,Wong FS,Wen Ldoi
10.1016/j.jaut.2015.08.019subject
Has Abstractpub_date
2016-01-01 00:00:00pages
76-88eissn
0896-8411issn
1095-9157pii
S0896-8411(15)30037-8journal_volume
66pub_type
杂志文章,评审abstract::Congenital immune deficiency states have often been valuable experimental models of nature that have significantly enhanced our understanding of the immune response. The relationship between CD4+, CD25+ and Treg cells in the induction of autoimmunity has attracted significant attention. We report herein a male child o...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.04.005
更新日期:2006-08-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune diseases. In both human and mouse SLE diseases, the autoimmune response targets a restricted set of autoantigens. Many of them are nucleic acids and proteins involved in the synthesis and processing of DNA or RNA, a characteristic which should ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1996.0031
更新日期:1996-04-01 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::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::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:BACKGROUND:Immune mediated diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD) commonly affect young and adolescent females. Anti-tumor necrosis factor (TNF)-α agents are increasingly used to treat these conditions, but their safety during pregnancy remains uncl...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.jaut.2016.11.004
更新日期:2017-01-01 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::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::We assessed the implication of Th (helper)-cells and the modulation of the Th1/Th2 dichotomy by n-3 polyunsaturated fatty acids (PUFA) in type I diabetic pregnancy (DP) and macrosomia. Female gestant rats fed a standard diet or n-3 PUFA regimen were rendered diabetic by administration of five low doses of streptozotoc...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.03.003
更新日期:2006-06-01 00:00:00
abstract::Nowadays, pharmacologic treatments of autoinflammatory diseases are largely palliative rather than curative. Most of them result in non-specific immunosuppression, which can be associated with broad disruption of natural and induced immunity with significant and sometimes serious unwanted injuries. Among the novel str...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2018.08.009
更新日期:2018-11-01 00:00:00
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 ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.03.001
更新日期:2019-06-01 00:00:00
abstract::A common epitope on S-antigen (arrestin), a potent autoantigen inducing experimental autoimmune uveoretinitis (EAU), and on human tumor necrosis factor alpha (hTNF alpha) was revealed using two monoclonal antibodies to S-antigen which inhibit EAU induction. The minimal common sequence for monoclonal antibody recogniti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80048-4
更新日期:1992-02-01 00:00:00
abstract::To explore the mechanisms underlying liver-directed autoimmune reactions in acute Hepatitis B Virus (HBV) infection, we followed five subjects who were identified in the early incubation phase (30-70 days before the first elevation of transaminases). We assessed serially cellular (using a T-lymphocyte migration inhibi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(88)90034-0
更新日期:1988-06-01 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:OBJECTIVE:To evaluate the efficacy and safety of biosimilars of anti-tumor necrosis factor (TNF)-α agents compared to their reference agents in immune mediated diseases. METHODS:Electronic databases were searched for randomized controlled trials (RCTs) assessing the efficacy and safety of biosimilars of anti-TNF-α age...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.jaut.2017.02.003
更新日期:2017-05-01 00:00:00
abstract::Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nerves evolving with diffuse sensory and motor symptoms. Although it is claimed that in neurodegenerative pathologies, a common feature is the failure of proteolytic systems to adequately eliminate aggregated or...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.05.009
更新日期:2018-08-01 00:00:00
abstract::IPEX syndrome is a congenital disorder of immune regulation caused by mutations in the FOXP3 gene, which is required for the suppressive function of naturally arising CD4 + CD25 + regulatory T cells. In this case series we evaluated serum samples from 12 patients with IPEX syndrome for the presence of common autoantib...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.06.017
更新日期:2010-11-01 00:00:00
abstract::Peptidyl arginine deiminases (PADs) catalyze a post-translational protein modification reaction called citrullination, where arginine is converted to citrulline. This modification has been linked to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). More recently, several studies have suggest...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2012.03.004
更新日期:2012-06-01 00:00:00
abstract::There is now convincing evidence for the imposition of self-tolerance by means of the clonal deletion of self-reactive T cells operating within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we have used transgen...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(92)90016-j
更新日期:1992-04-01 00:00:00
abstract::Glutamic acid decarboxylase 65 (GAD65) is a putative autoantigen associated with the pathogenesis of type 1 diabetes (T1D). The prevalence of autoreactive CD4+ T cells towards the immunodominant GAD65(555-567) epitope in DR4 healthy and T1D subjects was investigated with class II tetramers. A slightly higher percentag...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2005.08.007
更新日期:2005-12-01 00:00:00
abstract::Systemic lupus (SLE) is characterized by a break of B cell tolerance that plays a central role in disease pathophysiology. An early checkpoint defect occurs at the transitional stage leading to the survival of autoreactive B cells and consequently the production of pathogenic autoantibodies. The main purpose of our wo...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.05.002
更新日期:2019-08-01 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::The antigenic specificity of anti-phospholipid antibodies (APA) is a matter of intensive investigation. To further characterize these antibodies, we attempted to isolate human monoclonal APA. B-cells of patients with at least one positive test for antibodies against cardiolipin, phosphatidylserine, beta2-glycoprotein ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0316
更新日期:1999-09-01 00:00:00
abstract::The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with m...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0325
更新日期:1999-11-01 00:00:00
abstract::The primary immunodeficiency diseases (PIDs) include many genetic disorders that affect different components of the innate and adaptive responses. The number of distinct genetic PIDs has increased exponentially with improved methods of detection and advanced laboratory methodology. Patients with PIDs have an increased...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2019.01.011
更新日期:2019-05-01 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 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::There are two classes of autoimmune disease, organ-specific and non-organ specific or systemic. That cells producing autoantibodies are selected by antigen is strongly suggested by the presence of mutations and high affinity antibody. T-cells are pivotal in all forms of autoimmunity as evidenced by the therapeutic ben...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(92)90015-i
更新日期:1992-04-01 00:00:00
abstract::Dysregulation of autophagy has been implicated in the development of various disease indications including autoimmune diseases. Here we identified hitherto unsuspected molecular alterations of autophagy occurring at an early stage of the macroautophagy pathway in the salivary glands and spleen of NOD.H-2h4 mice that d...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102418
更新日期:2020-03-01 00:00:00
abstract::Antiphospholipid syndrome (APS) is characterized by thrombosis and pregnancy loss in the presence of antiphospholipid antibodies (aPL), mainly anticardiolipin, anti-beta2-glycoprotein I and lupus anticoagulant. However, similar to systemic lupus erythematosus, APS is also characterized by multiple other autoantibodies...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2007.11.011
更新日期:2008-02-01 00:00:00