Regulatory T cells and IFN-γ-producing Th1 cells play a critical role in the pathogenesis of Sjögren’s Syndrome
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ABSTRACT:
PROVIDER: PRJNA1064171 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27532319_1.fastq.gz | Fastqsanger.gz | |||
| SRR27532319_2.fastq.gz | Fastqsanger.gz | |||
| SRR27532320_1.fastq.gz | Fastqsanger.gz | |||
| SRR27532320_2.fastq.gz | Fastqsanger.gz | |||
| SRR27532321_1.fastq.gz | Fastqsanger.gz |
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Project description:Regulatory T cells and IFN-γ-producing Th1 cells play a critical role in the pathogenesis of Sjögren’s Syndrome
| PRJNA1066294 | ENA
Project description:Sjogren’s Disease (SjD) is an autoimmune disorder characterized by progressive inflammation and destruction of both salivary and lacrimal gland leading to dysfunction, as well as extra glandular manifestations. The etiology and pathophysiology of SjD are incompletely understood. Regulatory T (Treg) cells are critical for immunological tolerance. Although Treg abnormalities have been implicated in the pathogenesis of several autoimmune diseases, their role in SjD remains ambiguous. We had previously shown that the function and development of Treg cells depend on store-operated Ca2+ entry (SOCE), which is mediated by ORAI1 Ca2+ channels and stromal interaction molecules (STIM) 1 and 2 following T cell receptor (TCR) stimulation. The ablation of SOCE in Treg cells causes SjD-like disease with increased Th1 and interferon gene expression signatures in the inflamed salivary glands of mice. Here we show enhanced Th1 gene expression signatures and type I and II interferon responses in the peripheral blood mononuclear cells (PBMCs) of human patients with SjD compared to non-SjD controls. We also identified attenuated gene expression in memory Treg cells of patients with SjD. These data from mice and human patients provide new evidence for a critical role of Treg cells and IFNγ producing Th1 cells in the pathogenesis of SjD.
2024-11-04 | GSE253568 | GEO
Project description:Sjogren’s Disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, and extra glandular manifestations. The etiology and pathophysiology of SjD are incompletely understood. Regulatory T (Treg) cells are critical for immunological tolerance and although Treg abnormalities have been implicated in the pathogenesis of several autoimmune diseases, their role in SjD remains ambiguous. We here show that Stim1fl/flStim2fl/flFoxp3-Cre (Stim1/Stim2 Foxp3cre) mice develop a SjD-like phenotype, including severe sialadenitis with hyposalivation, lacrimal gland (LG) inflammation with dry eye and corneal damage, increased anti-Ro and anti-La autoantibody levels and interstitial lung disease. At the cellular level, salivary gland inflammation in Stim1/2Foxp3 mice is characterized by infiltration with CD4+ and CD8+ T cells, which is dominated by a T helper (Th) 1 and Th2 immune response. The changes in gene expression in SGs of mice correlate strongly with transcriptional and epigenetic dysregulation found in SjD patients. Our findings in Stim1/Stim2 Foxp3cre mice provide new evidence for a critical role of Treg cells and IFNγ producing Th1 cells in mediating SjD progression.
2024-11-04 | GSE253188 | GEO
Project description:Autoreactive T cells that infiltrate into the central nervous system (CNS) are believed to have a significant role in mediating the pathology of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of the neuroinflammatory process. Our previous work demonstrated that effectors secreted by Th1 and Th17 cells have different capacities to influence the phenotype and function of the glial cells. We have shown that Th1 effectors altered the phenotype and function of both microglia and astrocytes whereas Th17 effectors induced direct effects only on astrocytes but not on microglia. Here we investigated if effector molecules associated with IFN-g producing Th1 cells induced different gene expression profiles in microglia and astrocytes. We performed a microarray analysis of RNA isolated from microglia and astrocytes treated with medium and Th1 culture supernatants and compared the gene expression data. By using the criteria of 2-fold change and a false discovery rate of 0.01 (corrected p-value < 0.01), we demonstrated that a total of 2106 and 1594 genes were differentially regulated microglia and astrocytes respectively in response to Th1-derived factors. We observed that Th1 associated effectors induce distinct transcriptional changes in microglia and astrocytes in addition to commonly regulated transcripts. These distinct transcriptional changes regulate distinct physiological functions and this knowledge can help in better understanding of T cell mediated neuropathologies.
2018-12-03 | GSE113579 | GEO
Project description:Previously M3 muscarinic acetylcholine receptore (M3R) reactive Th1 cells were identified, and here, M3R reactive Th17 cells were identified in peripheral blood of primary Sjögren’s syndrome patients using ELISpot method. To assess TCR repertoire overlap between identified M3R reactive Th17 cells, and salivary gland infiltrating T cells, we performed high throughput TCR sequencing of those cells from pSS patient.
2021-04-18 | GSE148966 | GEO
Project description:T helper cell activation is highly regulated to ensure proper immune responses while avoiding autoimmune reactions. Cell functions are determined by regulation of various levels of gene expression including posttranslational modifications of proteins. Protein prenylation is a posttranslational modification, where either a farnesyl- or a geranylgeranyl residue is added to a protein. It was shown to play a role in the differentiation and activation of various T cell populations, including Th1 cells. However, it is largely unknown which proteins are prenylated in Th1 cells and what the effect of farnesyl transferase inhibitor treatment, which blocks farnesylation of proteins, on protein prenylation is in this context. Here, using mass spectrometry, we show the identification of farnesylated proteins in human Th1 cells. This approach additionally uncovered the farnesylation of proteins, not yet known to be prenylated. These data provide valuable insights into novel aspects of protein prenylation in Th1 cell activation and deepen our understanding of the effects of farnesyl transferase inhibitor treatment on the human immune system.
2025-01-18 | MSV000096890 | MassIVE
Project description:T helper cell activation is highly regulated to ensure proper immune responses while avoiding autoimmune reactions. Cell functions are determined by regulation of various levels of gene expression including posttranslational modifications of proteins. Protein prenylation is a posttranslational modification, which can be influenced by statin treatment and was shown to play a role in the differentiation and activation of various T cell populations, including Th1 cells. However, it is largely unknown which proteins are prenylated in Th1 cells and what the effect of statin treatment on protein prenylation is in this context. Here, using mass spectrometry, we show the comprehensive identification of prenylated proteins in human Th1 cells including changes during their activation, before analyzing the effect of statin treatment on this process. This approach additionally uncovered the prenylation of proteins, not yet known to be prenylated, including so far unknown motifs. These data provide valuable insights into novel aspects of protein prenylation in Th1 cell activation and deepen our understanding of the intended or unintended effects of statin treatment on the human immune system.
2024-08-12 | MSV000095575 | MassIVE
Project description:Control of the intracellular parasites that cause malaria and visceral leishmaniasis (VL) is dependent on the generation of pro-inflammatory, IFNγ+ Tbet+ CD4+ T (Th1) cells by infected hosts. Immunoregulatory IL-10 produced by Th1 cells serves to mitigate subsequent inflammation and related disease pathology. However, these IL-10-producing Th1 (Tr1) cells can also not only promote parasite persistence, but may impair immunity to re-infection and potential vaccine efficacy. Here, we identify molecular and phenotypic signatures that distinguish Th1 cells from Tr1 cells in both experimental VL, caused by infection of C57BL/6 mice with the human parasite Leishmania donovani, and in Plasmodium falciparum-infected humans participating in controlled human malaria infection (CHMI) studies. Such characterisations allow for the better understanding of Tr1 cell development and function in the context of these parasitic diseases, and for the identification of targets for immune modulation to improve anti-parasitic immunity.
| EGAS00001004454 | EGA
Project description:Autoreactive T cells that infiltrate into the central nervous system (CNS) are believed to have a significant role in mediating the pathology of neuroinflammatory diseases like multiple sclerosis. Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of neuroinflammatory processes. Our previous work demonstrated that effectors secreted by Th1 and Th17 cells have different capacities to influence the phenotype and function of glial cells. We have shown that Th1-derived effectors altered the phenotype and function of both microglia and astrocytes whereas Th17-derived effectors induced direct effects only on astrocytes but not on microglia. Here we investigated if effector molecules associated with IFN-γ producing Th1 cells induced different gene expression profiles in microglia and astrocytes. We performed a microarray analysis of RNA isolated from microglia and astrocytes treated with medium and Th-derived culture supernatants and compared the gene expression data. By using the criteria of 2-fold change and a false discovery rate of 0.01 (corrected p < 0.01), we demonstrated that a total of 2,106 and 1,594 genes were differentially regulated in microglia and astrocytes, respectively, in response to Th1-derived factors. We observed that Th1-derived effectors induce distinct transcriptional changes in microglia and astrocytes in addition to commonly regulated transcripts. These distinct transcriptional changes regulate peculiar physiological functions, and this knowledge can help to better understand T cell mediated neuropathologies.
| S-EPMC6191492 | biostudies-literature
Project description:Increasing evidence suggests that type 1 IFN (IFN-αβ) is associated with pathogenesis of Th1-mediated type 1 diabetes (T1D). A major source of IFN-αβ is plasmacytoid dendritic cells (pDCs). In this study, we analyzed peripheral blood pDC numbers and functions in at-risk, new-onset, and established T1D patients and controls. We found that subjects at risk for T1D and new-onset and established T1D subjects possessed significantly increased pDCs but similar number of myeloid DCs when compared with controls. pDC numbers were not affected by age in T1D subjects but declined with increasing age in control subjects. It was demonstrated that IFN-α production by PBMCs stimulated with influenza viruses was significantly higher in T1D subjects than in controls, and IFN-α production was correlated with pDC numbers in PBMCs. Of interest, only T1D-associated Coxsackievirus serotype B4 but not B3 induced majority of T1D PBMCs to produce IFN-α, which was confirmed to be secreted by pDCs. Finally, in vitro studies demonstrated IFN-α produced by pDCs augmented Th1 responses, with significantly greater IFN-γ-producing CD4(+) T cells from T1D subjects. These findings indicate that increased pDCs and their IFN-αβ production may be associated with this Th1-mediated autoimmune disease, especially under certain viral infections linked to T1D pathogenesis.
| S-EPMC4500116 | biostudies-literature