Tregs in autoimmune polyendocrine syndrome type I
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ABSTRACT:
PROVIDER: PRJNA1016308 | ENA |
REPOSITORIES: ENA
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Project description:Autoimmune polyendocrine syndrome type 1 (APS-1) relies on failures both in central and peripheral tolerance. A decreased number of regulatory T cells (Tregs) is repeatedly reported, and Tregs based therapy could therefore be considered. We have used a single cell transcriptomic approach to characterize Tregs sorted from blood.
2024-02-23 | GSE243061 | GEO
Project description:The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1
| PRJNA935743 | ENA
Project description:Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood. Methods: We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses. Results: Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients. Conclusions: Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
2025-01-28 | GSE225460 | GEO
Project description:The NOD (nonobese diabetic) mouse strain develops a characteristic autoimmune syndrome that closely resembles human type I diabetes. It has been suggested that NOD mice exhibit both numerical deficiency in CD4+CD25+ regulatory T cells (Treg) and reduced suppressive activity. We compared sorted CD4+CD25+ Tregs from the spleens of 6-7 week-old female NOD and nondiabetic B6.H2g7 mice. Tregs were 93±2% and 95±1% Foxp3+ in NOD and B6.H2g7 cells, respectively, on post-sort reanalysis. "Conventional" CD4+CD25- T cells (Tconv) are included as reference populations. Surprisingly, Treg "signature" is similar between the two strains, with only a few probesets that subtly deviate. Keywords: Cell population comparison from two mouse strains.
2008-12-19 | GSE6813 | GEO
Project description:The NOD (nonobese diabetic) mouse strain develops a characteristic autoimmune syndrome that closely resembles human type I diabetes. It has been suggested that NOD mice exhibit both numerical deficiency in CD4+CD25+ regulatory T cells (Treg) and reduced suppressive activity. We compared sorted CD4+CD25+ Tregs from the spleens of 6-7 week-old female NOD and nondiabetic B6.H2g7 mice. Tregs were 93±2% and 95±1% Foxp3+ in NOD and B6.H2g7 cells, respectively, on post-sort reanalysis. "Conventional" CD4+CD25- T cells (Tconv) are included as reference populations. Surprisingly, Treg "signature" is similar between the two strains, with only a few probesets that subtly deviate. Keywords: Cell population comparison from two mouse strains. For each strain (NOD and B6.g7), we analyzed two populations: CD4+CD25+ Treg and CD4+CD25- Tconv cells, for a total of four distinct populations. RNA from three mice were pooled for each replicate; there are three independent replicates for each population. After RMA normalization, intensity values were averaged across the three replicates and analyzed. We calculated the ratio of Treg/Tconv intensity values for each strain and compared the results.
2008-12-19 | E-GEOD-6813 | biostudies-arrayexpress
Project description:Macrophages are critical regulators of immune responses, and link innate immunity to acquired immunity. The precise mechanism of the pathogenesis of autoimmune diseases through tissue-resident macrophage is unclear. The role of the tissue-resident macrophages in the onset or development of autoimmunity was investigated using a murine model for Sjögren’s syndrome.
2018-02-21 | GSE110816 | GEO
Project description:Resident macrophage enhances an autoimmune lesion in Sjögren's syndrome
| PRJNA434644 | ENA
Project description:Transcriptome analysis of naïve Tregs, memory Tregs and CD161+ Tregs
| PRJNA489005 | ENA
Project description:The aim of the project is to do proteomic analysis of total cell lysate from rest and activated mouse Tregs. The proteomic data were mapped to the Gene Ontology Cellular Component (GOCC)database to obtain the list of membrane proteins on activated Tregs. The set of membrane proteins identified were compared with the potential Siglec-1 counter-receptors on activated Tregs.
2021-04-28 | PXD022259 | Pride
Project description:ATAC-seq data from naïve Tregs, memory Tregs and CD161+ Tregs
| PRJNA489004 | ENA