IL-6 Production Through Repression of UBASH3A Gene via Epigenetic Dysregulation of Super-Enhancer in CD4+T Cells in Rheumatoid Arthritis DOI Creative Commons
Kaoru Yamagata, Shingo Nakayamada, Tong Zhang

et al.

Research Square (Research Square), Journal Year: 2022, Volume and Issue: unknown

Published: Feb. 24, 2022

Abstract Background. UBASH3A as a negative regulator of T-cell receptors (TCRs) signaling is susceptible factor for rheumatoid arthritis (RA) patients who exhibit immune dysfunction. We studied expression in CD4 + T cells from healthy donors and RA patients, the involvement super-enhancer (SE) control expression, contribution to proinflammatory cytokine production. Methods. The mRNA protein levels were examined by quantitative PCR Western blotting, respectively. Locked nucleic acid was administered inhibit enhancer RNA (eRNA) expression. Factors recruited loci displaying SE architecture chromatin immunoprecipitation. transfected with plasmids, measured cytometric bead array. Results. lower than those donors. reduced eRNA_1 eRNA_3 knockdown. In BTB CNC homology 2 (BACH2), silencing transcription factor, accumulated at cells, whereas SE-defining mediator complex subunit 1 (MED1)/bromodomain 4 (BRD4), did not. However, opposite phenomena observed Although stimulation TCRs expressed on led interleukin (IL)-6 production, over-expression significantly inhibited its Conclusions. Transcription suppressed via epigenetic regulation patients. Decreased lead excessive activation TCR signaling, resulting enhanced production IL-6.

Language: Английский

An updated review on abnormal epigenetic modifications in the pathogenesis of systemic lupus erythematosus DOI Creative Commons
Xingyu Zhou, Shengnan Zhou, Yaping Li

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. The inconsistent prevalence of SLE between monozygotic twins suggests that environmental factors affect the occurrence this Abnormal epigenetic regulation strongly associated with pathogenesis SLE. Epigenetic mechanisms may be involved in development through DNA methylation, histone modification, noncoding RNAs, and other modifications. This review aims to show numerous studies as treasure map better understand effects aberrant modification onset SLE, which will benefit current basic research provide potential diagnostic biomarkers or therapeutic targets for

Language: Английский

Citations

1
Molecular mechanism of lncRNAs in pathogenesis and diagnosis of auto-immune diseases, with a special focus on lncRNA-based therapeutic approaches DOI

Amirreza Mehmandar‐Oskuie,

Kasra Jahankhani,

Arman Rostamlou

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 336, P. 122322 - 122322

Published: Dec. 1, 2023

Language: Английский

Citations

16
Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus DOI Creative Commons
Yi‐Giien Tsai, P. F. Liao,

Kai‐Hung Hsiao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 12, 2023

Systemic lupus erythematosus (SLE) is a heterogeneous multisystem inflammatory disease with wide variability in clinical manifestations. Natural arising CD4+ regulatory T cells (Tregs) play critical role maintaining peripheral tolerance by suppressing inflammation and preventing autoimmune responses SLE. Additionally, CD8+ cells, type 1 (Tr1), B also have less well-defined the pathogenesis of Elucidation roles various Treg subsets dedicated to immune homeostasis will provide novel therapeutic approach that governs for remission active lupus. Diminished interleukin (IL)-2 production associated depleted cell population, its reversibility IL-2 therapy provides important reasons treatment This review focuses on new therapeutics human low-dose benefits

Language: Английский

Citations

13
Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity DOI Creative Commons
Zhongyi Jiang, Haitao Zhu,

Pusen Wang

et al.

MedComm, Journal Year: 2022, Volume and Issue: 3(2)

Published: April 21, 2022

Abstract CD4 + CD25 regulatory T cells (Tregs), a subpopulation of naturally that characteristically express transcription factor Forkhead box P3 (FOXP3), play pivotal role in the maintenance immune homeostasis and prevention autoimmunity. With development biological technology, understanding plasticity stability Tregs has been further developed. Recent studies have suggested human are functionally phenotypically diverse. The functions mechanisms different phenotypes disease settings, such as tumor microenvironment, autoimmune diseases, transplantation, gradually become hot spots immunology research arouse extensive attention. Among complex functions, FOXP3 possess potent immunosuppressive capacity can produce various cytokines, IL‐2, IL‐10, TGF‐β, to regulate homeostasis. They alleviate progression diseases by resisting inflammatory responses, whereas promoting poor prognosis helping evade surveillance or suppressing effector activity. Therefore, methods for targeting their depleting them strengthen immunity expanding treat immunological need be Here, we discuss subpopulations essential immunotherapeutic strategies involving diseases.

Language: Английский

Citations

21
Loosening the Lid on Shoulder Osteoarthritis: How the Transcriptome and Metabolic Syndrome Correlate with End-Stage Disease DOI Open Access
Samuel J. Lynskey,

Z Ling,

Mark Ziemann

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3145 - 3145

Published: March 28, 2025

Metabolic syndrome (MetS) associated with Osteoarthritis (OA) is an increasingly recognised entity. Whilst the degenerative pattern in cuff-tear arthropathy (CTA) has been well documented, biological processes behind primary shoulder OA and CTA remain less understood. This study investigates transcriptomic differences these conditions, alongside impact of MetS patients undergoing total replacement. In a multi-centre study, 20 replacement were included based on specific treatment indications for as 25 rotator cuff repair (RCR) comparator group. Tissues from subchondral bone, capsule (OA RCR), synovium biopsied, RNA sequencing was performed using Illumina platforms. Differential gene expression conducted DESeq2, adjusting demographic factors, followed by pathway enrichment mitch package. Gene expressions differentially affected. showed mitochondrial dysfunction, GATD3A downregulation, increased cartilage degradation, while marked upregulated inflammatory catabolic pathways. The effect pathologies further shown. disrupted WNT/β-catenin signalling CTA, OA. Genes such ACAN, PANX3, CLU, VAT1L upregulated, highlighting potential biomarkers early detection. analysis reveals key between end-stage glenohumeral shows heightened metabolic/protein synthesis activity immune-driven inflammation. Under MetS, dysfunction (including downregulation) altered Wnt/β-catenin intensify bone damage. contrast, features strong complement activation, expression, collagen remodelling. worsens both conditions via oxidative stress, advanced glycation end products, ECM disruption—particularly, CS/DS degradation. These distinctions support targeted treatments, antioxidants Wnt modulators to aggrecanase inhibitors or clusterin augmentation. Addressing molecular disruptions, especially those amplified may preserve function, delay surgical intervention, improve long-term patient outcomes.

Language: Английский

Citations

0
LncRNAs involvement in pathogenesis of immune-related disease via regulation of T regulatory cells, an updated review DOI

Shayan Khalilollah,

Sina Kalantari Soltanieh,

Raed Obaid Saleh

et al.

Cytokine, Journal Year: 2024, Volume and Issue: 179, P. 156585 - 156585

Published: April 4, 2024

Language: Английский

Citations

2
LncRNA IL21‐AS1 interacts with hnRNPU protein to promote IL21 overexpression and aberrant differentiation of Tfh cells in systemic lupus erythematosus DOI Creative Commons
Limin Liu,

Longyuan Hu,

Haojun Long

et al.

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(12)

Published: Nov. 29, 2022

The aberrant differentiation of T follicular helper (Tfh) cells plays an important role in the pathogenesis systemic lupus erythematosus (SLE). However, mechanism regulating Tfh remains unclear. Long noncoding RNAs (lncRNAs) act as regulators processes innate and adaptive immune response. Whether lncRNAs are involved cell autoimmune responses need to be further identified.The characters functions human IL21-AS1 its mouse homologous lncRNA (mIl21-AS) were investigated by a series biochemical assays transfection assay. mIl21-AS1 humoral response vivo was explored keyhole limpet haemocyanin (KLH) chronic graft versus host disease (cGVHD) model.Human identified cloned. We uncovered that highly expressed CD4+ SLE patients cells, which promoted cells. Mechanistically, bound heterogeneous nuclear ribonucleoprotein U recruited acetyltransferases CREB-binding protein promoter IL21, leading transcriptional activation IL21 through increasing Histone H3 acetylation level on promoter. Moreover, proportion antibodies production significantly increased mIl21-AS knock-in mice immunized with KLH. overexpression also exacerbated lupus-like phenotype cGVHD model.Our results demonstrate activates transcription via epigenetic promote germinal centre response, adding insight into molecular regulation providing novel target for treatment.

Language: Английский

Citations

11
Immune Phenotype as a Biomarker for Systemic Lupus Erythematosus DOI Creative Commons
Shingo Nakayamada, Yoshiya Tanaka

Biomolecules, Journal Year: 2023, Volume and Issue: 13(6), P. 960 - 960

Published: June 8, 2023

The treatment of rheumatoid arthritis was revolutionized with the use molecular-targeted drugs that target immunoregulatory molecules. success these prompted development for systemic lupus erythematosus. However, erythematosus is a disease high heterogeneous immune abnormalities, and diverse cells or molecules can be targets. Thus, identification subpopulations based on abnormalities essential effective treatment. One analytical method used to identify immunophenotyping peripheral blood samples patients. This analysis evaluates validity cell subsets, which are expected developed as biomarkers precision medicine in appropriate targets set each subpopulation.

Language: Английский

Citations

6
IL-6 production through repression of UBASH3A gene via epigenetic dysregulation of super-enhancer in CD4+ T cells in rheumatoid arthritis DOI Creative Commons
Kaoru Yamagata, Shingo Nakayamada, Tong Zhang

et al.

Inflammation and Regeneration, Journal Year: 2022, Volume and Issue: 42(1)

Published: Nov. 3, 2022

Rheumatoid arthritis (RA) is associated with immune dysfunction. UBASH3A as a negative regulator of T cell receptors (TCRs) signaling susceptible factor in RA. The aim this study was to determine the role RA pathogenesis, by assessing super-enhancer (SE) control expression CD4+ cells and contribution latter proinflammatory cytokine production patients RA.UBASH3A mRNA protein levels were quantified PCR western blotting, respectively. treated locked nucleic acid inhibit enhancer RNA (eRNA) expression. Chromatin immunoprecipitation used identify factors recruited loci displaying SE architecture. transfected plasmids, measured cytometric bead array.UBASH3A extracted susceptibility gene SNPs SEs that are highly expressed silico screening. lower than control. eRNA_1 eRNA_3 knockdown reduced levels. exhibited accumulation BTB CNC homology 2 (BACH2), silencing transcription factor, at cells, but not SE-defining mediator complex subunit 1 (MED1)/bromodomain 4 (BRD4). However, opposite changes observed Stimulation TCRs on resulted interleukin (IL)-6 production, while over-expression significantly inhibited production.In RA, suppressed via epigenetic regulation cells. Low result excessive TCR signal activation subsequent enhancement IL-6 production.

Language: Английский

Citations

10
Long non‐coding RNAs in systemic lupus erythematosus: New insights into disease pathogenesis and diagnosis DOI
Xin Chen, Qi Cheng, Huaxiang Wu

et al.

Scandinavian Journal of Immunology, Journal Year: 2022, Volume and Issue: 95(6)

Published: March 22, 2022

Systemic lupus erythematosus (SLE) is a remarkable heterogeneous autoimmune disease that sometimes hard to diagnose at the early stage and can lead premature mortality. Long non-coding RNAs (lncRNAs) are class of non-protein-coding greater than 200 nucleotides in length regulate gene expression various human diseases, including SLE. Peripheral blood samples renal tissue from SLE patients were used for study. Abnormally expressed lncRNAs have been shown influence several signalling pathways, IFN-I, MAPK WNT pathways. This affect cellular phenotypes like cell activation, differentiation skewing, cytokine production apoptosis. Many reported may be useful diagnosing, evaluating progression predicting potential organ damage patients. While numerous play important roles SLE, more basic clinical studies warranted clarify function these regulatory molecules determine their diagnostic value.

Language: Английский

Citations

8