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 hyper-inflammation during the acute phase and the hypo-inflammation during immunosuppressive phase of sepsis. However, the mechanisms for controlling hypo-inflammatory response in endotoxin tolerant macrophages remain to be fully understood. Considering that metabolic control of inflammation is an emerging field and the balance between AMP/ATP and oxidized NAD+/reduced NADH is associated with inflammation and metabolism, we analyzed the level of NAD+ in TLR-triggered innate inflammatory response, and found that the decreased level of NAD+ was significantly related to the increased inflammatory cytokine production both in vivo and in vitro. By screening the expression and function of NAD+ dependent type III deacetylase Sirtuin family members, we found that SIRT5 and SIRT1/2 had opposite expression patterns and functions in macrophages. SIRT5 deficiency decreased TLR-triggered inflammation in both acute and immunosuppressive phases of sepsis. Interestingly, cytoplasmic SIRT5 counteracted the inhibitory effects of SIRT2 and enhanced the innate inflammatory responses in macrophages and even in endotoxin-tolerant macrophages by promoting acetylation of p65 and activation of NF-κB pathway. Mechanistically, SIRT5 competed with SIRT2 to interact with NF-κB p65, in a deacetylase activity-independent way, to block the deacetylation of p65 by SIRT2, which consequently led to increased acetylation of p65 and the activation of NF-κB pathway and its downstream cytokines. Our study discovered the new functions of different Sirtuin members in sepsis, indicating that targeting of Sirtuin family members at different sepsis phases can be helpful to precisely control the progression of sepsis.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Qin K,Han C,Zhang H,Li T,Li N,Cao Xdoi
10.1016/j.jaut.2017.04.006subject
Has Abstractpub_date
2017-07-01 00:00:00pages
120-129eissn
0896-8411issn
1095-9157pii
S0896-8411(17)30238-Xjournal_volume
81pub_type
杂志文章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: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::Isolated congenital heart block may be associated with autoimmune disorder such as Sjögren Syndrome and systemic lupus erythematosus. In this work we demonstrate circulating autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor (mAChR) in the sera of children with congenital heart block. This anti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2000.0461
更新日期:2001-03-01 00:00:00
abstract::Multiple sclerosis (MS), an inflammatory and demyelinating autoimmune disease of CNS has both, a genetic and an environmental predisposition. Among all the genetic factors associated with MS susceptibility, HLA class II haplotypes such as DR2/DQ6, DR3/DQ2, and DR4/DQ8 show the strongest association. Although a direct ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2011.05.001
更新日期:2011-09-01 00:00:00
abstract::Our aim was to investigate presence of tumour necrosis factor (TNF) and interleukin (IL)-10 in serum and their relation to different genotypes as well as to clinical and laboratory phenotypes in patients with polymyositis and dermatomyositis. In 65 patients with poly- or dermatomyositis the inflammatory cytokine balan...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.06.003
更新日期:2006-08-01 00:00:00
abstract::Counter-balancing regulatory mechanisms, such as the induction of regulatory T cells (Treg), limit the effects of autoimmune attack in neuroinflammation. However, the role of dendritic cells (DCs) as the most powerful antigen-presenting cells, which are intriguing therapeutic targets in this context, is not fully unde...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.09.008
更新日期:2017-01-01 00:00:00
abstract::A primary initiating epitope in the NOD mouse model of Type 1 Diabetes (T1D) lies between residues 9 and 23 of the insulin B chain. The B:9-23 peptide can bind to the NOD MHC class II molecule (I-Ag7) in multiple registers, but only one, (register 3, R3), creates complexes able to stimulate the majority of pathogenic ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.08.004
更新日期:2019-01-01 00:00:00
abstract::The probability that epitope spreading occurs in multiple sclerosis (MS) and the fact that patients have been shown to respond to multiple myelin epitopes concurrently makes the use of peptide-specific tolerance therapies targeting single epitopes problematic. To attempt to overcome this limitation, we have employed c...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.12.002
更新日期:2006-12-01 00:00:00
abstract::Peripheral T cells can be polarized towards type 1 or type 2 cytokine immune responses during TCR engagement. Because T cell selection by peptide plus self-MHC in the thymus requires TCR engagement, we hypothesized that type 1 cytokines may polarize developing T cells. We cultured thymi from BBDR rats in adult thymus ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(02)00091-4
更新日期:2003-02-01 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::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::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::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::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::Helper T cells are required for development of the autoantibody responses to native mouse erythrocytes (MRBC) that spontaneously develop in NZB mice. However, the stimulus for these Th is not known. Therefore, we compared the abilities of splenic T cells from actively autoimmune old NZB mice and preautoimmune, young N...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0062
更新日期:1996-08-01 00:00:00
abstract::Previous studies have demonstrated increased expression of a laminin-like protein in labial salivary glands from Sjögren's syndrome (SS) patients. The objective of the present study was to verify the identity of this protein and to compare lymphocytic infiltration and laminin expression in minor salivary gland ductal ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0109
更新日期:1997-02-01 00:00:00
abstract::The standard treatment of thrombosis related to antiphospholipid antibodies is lifelong high-intensity oral anticoagulation. This standard is primarily based on retrospective evaluations of such patients. In this paper we give a summary of current treatment of deep leg vein thrombosis, pulmonary embolism, ischaemic st...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.2000.0395
更新日期:2000-09-01 00:00:00
abstract::There is significant unmet need in the treatment of lupus nephritis (LN) patients. In this review, we highlight the role of the TWEAK/Fn14 pathway in mediating key pathologic processes underlying LN involving both glomerular and tubular injury, and thus the potential for renal protection via blockade of this pathway. ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2012.05.003
更新日期:2012-09-01 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::The serum concentrations of IgM, IgG1, IgG2b, IgG3 and IgA were determined in mice of C57BL/6 background, from weaning to one year of age, by quantitative isotype-specific, indirect double sandwich enzyme-linked immunosorbent assays (ELISAs). Only limited data could be obtained for the IgG2a isotype in the present stu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(89)90013-9
更新日期:1989-12-01 00:00:00
abstract::Salivary gland (SG) acinar-cells are susceptible to endoplasmic reticulum (ER) stress related to their secretory activity and the complexity of synthesized secretory products. SGs of Sjögren's syndrome patients (SS)-patients show signs of inflammation and altered proteostasis, associated with low IRE1α/XBP-1 pathway a...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.07.006
更新日期:2016-12-01 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::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::Selective homing of autoreactive lymphocytes to the pancreatic islets of Langerhans is essential for triggering the cascade of molecular and cellular interactions which culminate in the specific destruction of the insulin-producing beta-cells. Based upon the sequential multistep model of lymphocyte adhesion to the end...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1069
更新日期:1994-12-01 00:00:00
abstract::Increasing evidence suggests that immune complexes made of anti-nuclear antibodies bound to nucleosomes released from dead cells play an important role in the pathogenesis of lupus nephritis. However, the nature and composition of apoptotic nucleosomes still remain elusive. Since large amounts of nucleosomes are relea...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1997.0172
更新日期:1998-02-01 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::The biology of hematopoietic stem cell (HSC) is a current topic of interest which has important implications for clinical HSC transplantation as well as for the basic research of HSC. The most primitive HSCs in mammals, including mice and humans, have long been believed to be CD34 antigen (Ag)-positive (CD34(+)) cells...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2007.12.004
更新日期:2008-05-01 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
abstract::Epitope spreading is an important mechanism for the development of autoantibodies (autoAbs) in autoimmune diseases. The study of epitope spreading in human autoimmune diseases is limited due to the major challenge of identifying the initial/primary target epitopes on autoantigens in autoimmune diseases. We have been s...
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
abstract::Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2015.07.006
更新日期:2015-09-01 00:00:00