Abstract:
:Systemic lupus erythematosus (SLE) is an autoimmune disease primarily afflicting women. The reason for the gender bias is unclear, but genetic susceptibility, estrogen and environmental agents appear to play significant roles in SLE pathogenesis. Environmental agents can contribute to lupus susceptibility through epigenetic mechanisms. We used (C57BL/6xSJL)F1 mice transgenic for a dominant-negative MEK (dnMEK) that was previously shown to be inducibly and selectively expressed in T cells. In this model, induction of the dnMEK by doxycycline treatment suppresses T cell ERK signaling, decreasing DNA-methyltransferase expression and resulting in DNA demethylation, overexpression of immune genes Itgal (CD11a) and Tnfsf7 (CD70), and anti-dsDNA antibody. To examine the role of gender and estrogen in this model, male and female transgenic mice were neutered and implanted with time-release pellets delivering placebo or estrogen. Doxycycline induced IgG anti-dsDNA antibodies in intact and neutered, placebo-treated control female but not male transgenic mice. Glomerular IgG deposits were also found in the kidneys of female but not male transgenic mice, and not in the absence of doxycycline. Estrogen enhanced anti-dsDNA IgG antibodies only in transgenic, ERK-impaired female mice. Decreased ERK activation also resulted in overexpression and demethylation of the X-linked methylation-sensitive gene CD40lg in female but not male mice, consistent with demethylation of the second X chromosome in the females. The results show that both estrogen and female gender contribute to the female predisposition in lupus susceptibility through hormonal and epigenetic X-chromosome effects and through suppression of ERK signaling by environmental agents.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Strickland FM,Hewagama A,Lu Q,Wu A,Hinderer R,Webb R,Johnson K,Sawalha AH,Delaney C,Yung R,Richardson BCdoi
10.1016/j.jaut.2011.11.001subject
Has Abstractpub_date
2012-05-01 00:00:00pages
J135-43issue
2-3eissn
0896-8411issn
1095-9157pii
S0896-8411(11)00108-9journal_volume
38pub_type
杂志文章abstract::The use of autoantigen-specific regulatory T cells (Tregs) as a cellular therapy for autoimmune diseases is appealing. However, it is challenging to isolate and expand large quantity of Tregs expressing disease-relevant T-cell receptors (TCR). To overcome this problem, we used an approach aiming at redirecting the spe...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
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abstract::Polymyositis is classified as a separate entity among idiopathic inflammatory myopathies but it is considered as the least common since it is an exclusion diagnosis. This myopathy usually presents with subacute-chronic symmetric proximal limb weakness, although some extramuscular manifestations are common. Creatine ki...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2014.01.025
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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
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0297
更新日期:1999-08-01 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
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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::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::This paper describes some of the methodological problems related to the measurement of cyclosporin. The clinical value of the measurements following organ transplantation are discussed and those areas also applying to autoimmune indications are highlighted. It is concluded that the routine use of cyclosporin monitorin...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(92)90032-l
更新日期:1992-04-01 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.2009.12.001
更新日期:2010-05-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2003.08.002
更新日期:2003-12-01 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
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journal_title:Journal of autoimmunity
pub_type: 社论,历史文章
doi:10.1016/j.jaut.2013.12.019
更新日期:2014-02-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.02.004
更新日期:2018-06-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102561
更新日期:2021-01-01 00:00:00
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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
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2000.0388
更新日期:2000-08-01 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.2018.11.001
更新日期:2019-01-01 00:00:00
abstract::Nodding Syndrome (NS) is a fatal pediatric epilepsy of unknown etiology, accompanied by multiple neurological impairments, and associated with Onchocerca volvulus (Ov), malnutrition, war-induced trauma, and other insults. NS patients have neuroinflammation, and ~50% have cross-reactive Ov/Leiomodin-1 neurotoxic autoim...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102462
更新日期:2020-08-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2014.01.002
更新日期:2014-05-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(02)00091-4
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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
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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
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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
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0258
更新日期:1999-03-01 00:00:00
abstract::Natural autoantibodies (autoNAb) recognize self antigens and are an important component of the immune system, as species ranging from invertebrates to vertebrates have polyreactive IgM NAbs. In higher vertebrates, different polyreactive autoNAbs isotypes are also frequently encountered and autopolyreactive IgG NAbs ar...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2013.01.006
更新日期:2013-03-01 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
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(91)90178-f
更新日期:1991-08-01 00:00:00
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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
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2002.0590
更新日期:2002-06-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章,meta分析
doi:10.1016/j.jaut.2008.02.002
更新日期:2008-08-01 00:00:00