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 rescued from disease entirely. Using fetal thymus organ culture (FTOC) as a model of T cell development and an associated in vitro T1DM model, we set out to reconcile the role of TNF-alpha in thymic development with its role in the pathogenesis of T1DM. Our data indicate that NOD derived FTOC produce a smaller percentage of double negative (CD4(-)/CD8(-)) thymocytes expressing TNF receptors compared to non-diabetic C57BL/6 (B6) derived FTOC. NOD FTOC produce more TNF-alpha than B6 FTOC during days 6-9 of culture, a time when negative selection of T cells is known to occur. Neutralization of this endogenous TNF-alpha production in NOD derived FTOC with soluble TNF receptor (sTNF R1) rescued insulin production in our in vitro T1DM model. Flow cytometric analysis of NOD FTOC treated with recombinant TNF-alpha (rTNF-alpha) or sTNF R1 demonstrated that the relative levels of TNF-alpha in the culture during the selection window (days 6-9) influence the ratio of immature vs. mature T cells that emerge from FTOC.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Middlebrook AJ,Lebsack T,DeLuca Ddoi
10.1016/j.jaut.2007.06.002subject
Has Abstractpub_date
2007-09-01 00:00:00pages
134-45issue
2-3eissn
0896-8411issn
1095-9157pii
S0896-8411(07)00071-6journal_volume
29pub_type
杂志文章abstract::The features of autoantibodies (autoAb) to liver fumarylacetoacetate hydrolase (FAH) elicited in mice infected with mouse hepatitis virus (MHV) were studied by ELISA and western-blot competition assays. All sera tested contained Ab to cryptic FAH epitopes according with results from western-blot tests, whereas ELISA d...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.05.006
更新日期:2004-09-01 00:00:00
abstract::We have investigated the pathophysiological basis of cardiac dysfunction in autoimmune myocarditis and in the resulting dilated cardiomyopathy. To this end we utilized the myosin-induced autoimmune myocarditis model in BALB/c mice. Myocarditis has been found to be associated with massive ventricular lymphocyte infiltr...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0273
更新日期:1999-05-01 00:00:00
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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::In this study, we assessed the expression of activation markers on gammadelta T cells in central nervous system (CNS) lesions of SJL mice adoptively sensitized to develop experimental autoimmune encephalomyelitis (EAE) using myelin basic protein-reactive T cells. Although disease expression is known to be dependent up...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0547
更新日期:2001-12-01 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::Systemic lupus erythematosus (SLE) patients often have continuous production of interferon-alpha (IFN-alpha), but production of in vitro IFN-alpha by peripheral blood mononuclear cells (PBMC) may be varyingly reduced. We here report that IFN-alpha production induced by Herpes simplex virus (HSV) in PBMC resembling imm...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0215
更新日期:1998-10-01 00:00:00
abstract::Genetic abnormalities predisposing to autoimmunity generally act in a cooperative manner affecting one or several mechanisms regulating immunological tolerance. In addition, many of these genetic abnormalities are also involved in the development of lymphoproliferative diseases. In the present study, we have determine...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.07.002
更新日期:2010-12-01 00:00:00
abstract::Many years of work, multiplex family collection and endless genotyping finally give fruit. The original aim cannot be lost. The aim is not only to identify mutations involved in susceptibility for systemic lupus erythematosus (SLE) but to elucidate the disease pathogenesis as well. After genetics comes the biology. We...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/s0896-8411(03)00093-3
更新日期:2003-09-01 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
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80037-x
更新日期:1990-12-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2009.05.003
更新日期:2010-03-01 00:00:00
abstract::Peptidomimetic compounds that bind to major histocompatibility complex class II molecules and are resistant to cathepsins can competitively inhibit the presentation of processed protein antigens. Therefore, compounds that bind to autoimmune disease-associated class II molecules are expected to compete with autoantigen...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.09.005
更新日期:2006-11-01 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::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::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
abstract::Immunoblotting was optimized to detect autoantibodies to TSH receptors from human and porcine thyroid tissue and to determine their epitope specificity. Autoantibodies to putative TSH receptor proteins in thyroid particulate membranes were detected in approximately 35% of sera from patients with Graves' disease. Howev...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(91)90164-8
更新日期:1991-06-01 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::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::Previous studies on Spanish patients with Primary Biliary Cirrhosis (PBC) have shown extensive, disease-specific cross-reactivity between the 65-kDa heat shock protein (hsp65) of Mycobacterium gordonae and pyruvate dehydrogenase complex-E2 (PDC-E2), the major target of anti-mitochondrial antibody (AMA). Studies on a B...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.03.002
更新日期:2004-06-01 00:00:00
abstract:OBJECTIVE:Gut dysbiosis has been reported implicated in ankylosing spondylitis (AS), a common chronic inflammatory disease mainly affects sacroiliac joints and spine. Utilizing deep sequencing on the feces of untreated AS patients, our study aimed at providing an in-depth understanding of AS gut microbiota. METHODS:We...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.102360
更新日期:2020-02-01 00:00:00
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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::Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthropathy of childhood. Juvenile idiopathic arthritis is believed to be a complex genetic trait influenced by both genetic and environmental factors. Twin and family studies suggest a substantial role for genetic factors in the predispositio...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2015.08.002
更新日期:2015-11-01 00:00:00
abstract::Diabetes in the non-obese diabetic (NOD) mouse is a multigenic autoimmune disease and is possibly controlled by three recessive loci, including one that is linked to the major histocompatibility complex (MHC). The first external domain of the Class II MHC I-A beta chain in these mice is unique and has been suggested a...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80017-4
更新日期:1990-10-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contri...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2014.08.003
更新日期:2015-01-01 00:00:00
abstract::Chronic myocarditis often progresses to dilated cardiomyopathy resulting in heart failure or cardiac transplantation. Viral infection is the most common cause of myocarditis and coxsackie B viruses (CBV) are the most frequently cited etiologic agents associated with myocarditis and cardiomyopathy. Additionally, CBV in...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2005.05.007
更新日期:2005-09-01 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::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::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::Interventional approaches that have been successful in delaying insulin-dependent diabetes mellitus (IDDM) using antigen-based immunotherapies include parenteral immunization. It has potential for clinical application provided that effective adjuvants suitable for human use can be found. We have previously shown that ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0047
更新日期:1996-06-01 00:00:00
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