Tregs in autoimmune polyendocrine syndrome type I
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE243061 | GEO | 2024/02/23
REPOSITORIES: GEO
Similar Datasets
Project description:Tregs in autoimmune polyendocrine syndrome type I
| PRJNA1016308 | ENA
Project description:The aim of the study was to test the hypothesis that APS-1 patient sera contains IgG reactivity to serum factor antigens concomitant with prototypical autoimmne antigens. We diluted patient sera 1:250 and incubated dilutions on a nitrocellulose-platform array printed with whole protein antigens. In this study, serum from 14 ndividuals (subsetted into APS-1 patient and healthy control categories) was profiled for IgG autoantibody reactivity to whole protein autoimmune and serum factor antigens. APS-1 patient sera was found using the significance analysis of microarrays (SAM) algorithm to be significantly more reactive with prototypical cytokine antigens previously identified as targets of autoantibodies.
2013-09-24 | E-GEOD-51101 | biostudies-arrayexpress
Project description:Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thromboembolic events and pregnancy loss. We sought to characterize the DNA methylation profile of primary APS in comparison to healthy controls and individuals with SLE.
2019-01-02 | GSE124565 | GEO
Project description:Donminant negative transform growth factor receptor II (DNR) mice were served as a murine primary biliary cirrhrosis model. CD4+Foxp3+ Regulatory T cells (Tregs) play a critical role in self-tolerance and in regulating PBC. In order to determine whether DNR mice derived Tregs processed defective function compared with WT Tregs, CD4+Foxp3+ Treg cells were sorted from DNR and WT mice, respectively, then gene expression analysis was performed by using the Affymetrix GeneChip Mouse Genome 430 2.0 arrays CD4+Foxp3+ Tregs were sorted from the spleen of 10-week-old DNR mice and B6 wild-type mice, respectively. RNA of each sample was then extracted and hybridized on Affymetrix microarrays to detail differences between DNR Tregs and WT Tregs in gene expression.
2014-11-05 | E-GEOD-62964 | biostudies-arrayexpress
Project description:This is system 2, the model with Michelis Menten type antigen uptake by pAPCs, described in the article:
Self-tolerance and Autoimmunity in a Regulatory T Cell Model.
Alexander HK, Wahl LM. Bull Math Biol.
2010 Mar 2.
PMID: 20195912
, doi: 10.1007/s11538-010-9519-2
;
Abstract:
The class of immunosuppressive lymphocytes known as regulatory T cells (Tregs) has been identified as a key component in preventing autoimmune diseases. Although Tregs have been incorporated previously in mathematical models of autoimmunity, we take a novel approach which emphasizes the importance of professional antigen presenting cells (pAPCs). We examine three possible mechanisms of Treg action (each in isolation) through ordinary differential equation (ODE) models. The immune response against a particular autoantigen is suppressed both by Tregs specific for that antigen and by Tregs of arbitrary specificities, through their action on either maturing or already mature pAPCs or on autoreactive effector T cells. In this deterministic approach, we find that qualitative long-term behaviour is predicted by the basic reproductive ratio R (0) for each system. When R (0) 1, this equilibrium loses its stability and a stable non-trivial equilibrium appears. We interpret the absence of self-damaging populations at the trivial equilibrium to imply a state of self-tolerance, and their presence at the non-trivial equilibrium to imply a state of chronic autoimmunity. Irrespective of mechanism, our model predicts that Tregs specific for the autoantigen in question play no role in the system's qualitative long-term behaviour, but have quantitative effects that could potentially reduce an autoimmune response to sub-clinical levels. Our results also suggest an important role for Tregs of arbitrary specificities in modulating the qualitative outcome. A stochastic treatment of the same model demonstrates that the probability of developing a chronic autoimmune response increases with the initial exposure to self antigen or autoreactive effector T cells. The three different mechanisms we consider, while leading to a number of similar predictions, also exhibit key differences in both transient dynamics (ODE approach) and the probability of chronic autoimmunity (stochastic approach).
Originally created by libAntimony v1.4 (using libSBML 3.4.1)
2024-09-02 | BIOMD0000000290 | BioModels
Project description:This is system 1, the model with linear antigen uptake by pAPCs, described in the article:
Self-tolerance and Autoimmunity in a Regulatory T Cell Model.
Alexander HK, Wahl LM.
Bull Math Biol. 2010 Mar 2.
PMID:20195912, doi:10.1007/s11538-010-9519-2;
Abstract:
The class of immunosuppressive lymphocytes known as regulatory T cells (Tregs) has been identified as a key component in preventing autoimmune diseases. Although Tregs have been incorporated previously in mathematical models of autoimmunity, we take a novel approach which emphasizes the importance of professional antigen presenting cells (pAPCs). We examine three possible mechanisms of Treg action (each in isolation) through ordinary differential equation (ODE) models. The immune response against a particular autoantigen is suppressed both by Tregs specific for that antigen and by Tregs of arbitrary specificities, through their action on either maturing or already mature pAPCs or on autoreactive effector T cells. In this deterministic approach, we find that qualitative long-term behaviour is predicted by the basic reproductive ratio R (0) for each system. When R (0) 1, this equilibrium loses its stability and a stable non-trivial equilibrium appears. We interpret the absence of self-damaging populations at the trivial equilibrium to imply a state of self-tolerance, and their presence at the non-trivial equilibrium to imply a state of chronic autoimmunity. Irrespective of mechanism, our model predicts that Tregs specific for the autoantigen in question play no role in the system's qualitative long-term behaviour, but have quantitative effects that could potentially reduce an autoimmune response to sub-clinical levels. Our results also suggest an important role for Tregs of arbitrary specificities in modulating the qualitative outcome. A stochastic treatment of the same model demonstrates that the probability of developing a chronic autoimmune response increases with the initial exposure to self antigen or autoreactive effector T cells. The three different mechanisms we consider, while leading to a number of similar predictions, also exhibit key differences in both transient dynamics (ODE approach) and the probability of chronic autoimmunity (stochastic approach).
Originally created by libAntimony v1.4 (using libSBML 3.4.1)
2024-09-02 | BIOMD0000000289 | BioModels
Project description:Autoimmune regulator (Aire) and TGF-β signaling play an important role in central tolerance and peripheral tolerance respectively, by eliminating or suppressing the activity of autoreactive T cells. We have previously demonstrated that dnTGFβRII mice develop a defect in peripheral tolerance and a primary biliary cirrhosis (PBC) like disease. We hypothesized that by introducing the AIRE gene to this model, we would observe a more severe PBC phenotype. Interestingly, however, we demonstrate that while dnTGFβRII Aire-/- mice do manifest key histologic and serologic features of autoimmune cholangitis, they also develop mild to moderate interface hepatitis and show high levels of alanine transaminase (ALT) and antinuclear antibodies (ANA), characteristics of autoimmune hepatitis (AIH). To further understand this unique phenotype, we performed RNA-seq and flow cytometry to explore the functional pathways and immune cell pathways in the liver of dnTGFβRII Aire-/- mice. Our data revealed enrichments of programmed cell death pathways and predominant CD8+ T cell infiltrates. Depleting CD8+ T cells using an anti-CD8α antibody significantly alleviated hepatic inflammation and prolonged the lifespan of these mice. Finally, RNA-seq data indicated the clonal expansion of hepatic CD8+ T cells. In conclusion, these mice develop an autoreactive CD8+ T cell mediated autoimmune cholangitis with concurrent hepatitis that exhibits key histological and serological features of the AIH-PBC overlap syndrome, representing a novel model for the study of tolerance and autoimmune liver disease.
2023-02-21 | GSE223894 | GEO
Project description:Regulatory T cells (Tregs) expressing the transcription factor Foxp3 have a pivotal role in maintaining immunological self-tolerance1-5; yet, excessive Treg activities suppress anti-tumor immune responses6-8. Compared to resting phenotype Tregs (rTregs) in the secondary lymphoid organs, Tregs in non-lymphoid tissues including solid tumors exhibit an activated Treg (aTreg) phenotype9-11. However, aTreg function and whether its generation can be manipulated to promote tumor immunity without evoking autoimmunity are largely unexplored. Here we show that the transcription factor Foxo1, previously demonstrated to promote Treg suppression of lymphoproliferative diseases12,13, has an unexpected function in inhibiting aTreg-mediated immune tolerance. We found that aTregs turned over at a slower rate than rTregs, but were not locally maintained in tissues. Transcriptome analysis revealed that aTreg differentiation was associated with repression of Foxo1-dependent gene transcription, concomitant with reduced Foxo1 expression, cytoplasmic Foxo1 localization, and enhanced Foxo1 phosphorylation at sites of the Akt kinase. Treg-specific expression of an Akt-insensitive Foxo1 mutant prevented downregulation of lymphoid organ homing molecules, and impeded Treg homing to non-lymphoid organs, causing CD8+ T cell-mediated autoimmune diseases. Compared to Tregs from healthy tissues, tumor-infiltrating Tregs downregulated Foxo1 target genes more substantially. Expression of the Foxo1 mutant at a lower dose was sufficient to deplete tumor-associated Tregs, activate effector CD8+ T cells, and inhibit tumor growth without inflicting autoimmunity. Thus, Foxo1 inactivation is essential for the migration of aTregs that have a crucial function in suppressing CD8+ T cell responses; and the Foxo signaling pathway in Tregs can be titrated to preferentially break tumor immune tolerance.
2015-11-15 | GSE74957 | GEO
Project description:Antiphospholipid syndrome (APS) is a rheumatic inflammatory chronic autoimmune disease inducing hypercoagulable state associated with vascular thrombosis and pregnancy loss in women. Cardiac, cerebral and vascular strokes in these patients are responsible for reduction in life expectancy. Timely diagnosis and accurate monitoring of disease are decisive to improve the accuracy of therapy. In the present work, we present a NMR-based metabolomic study of blood sera of APS patients. Our data show that individuals suffering APS have a characteristic metabolomic profile with abnormalities associated to the metabolism of methyl group donors, ketone bodies and amino acids. We have identified for the first time the metabolomic fingerprint characterizing APS disease having potential application to improve APS timely diagnosis and appropriate therapeutic approaches.
2017-09-06 | MTBLS356 | MetaboLights
Project description:Autoimmune diseases such as multiple sclerosis (MS) develop because of failed peripheral immune tolerance for a specific self-antigen (Ag). Numerous approaches for Ag-specific suppression of autoimmune neuroinflammation have been proven in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. One such approach is intravenous (i.v.) tolerance induction by injecting a myelin Ag used for EAE induction. However, the translation of this and similar experimental strategies into therapy for MS has been hampered by uncertainty regarding relevant myelin Ags in MS patients. To address this issue, we developed a therapeutic strategy that relies on oligodendrocyte (Ol)-derived extracellular vesicles (Ol-EVs), which naturally contain multiple myelin Ags. Ol-EVs injected i.v. suppressed disease in a myelin Ag-dependent manner, both prophylactically and therapeutically, in several EAE models. The treatment was safe and restored immune tolerance by inducing immunosuppressive monocytes and apoptosis of autoreactive encephalitogenic CD4+ T cells. Finally, we show that human Ols also release EVs containing most relevant myelin Ags, providing a basis for their use in MS therapy. These findings introduce an approach for suppressing central nervous system autoimmunity in a myelin Ag-specific manner.
2020-05-17 | MSV000085434 | MassIVE