Epigenetic regulation of B cells and its role in autoimmune pathogenesis

Cellular and Molecular Immunology, Год журнала: 2022, Номер 19(11), С. 1215 - 1234

Опубликована: Окт. 12, 2022

Abstract B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although previous studies have shown many genetic polymorphisms associated with B-cell activation patients various disorders, progress epigenetic research has revealed new mechanisms leading to hyperactivation. Epigenetic mechanisms, including those involving histone modifications, DNA methylation, and noncoding RNAs, regulate responses, their dysregulation can contribute Patients diseases show alterations that lead initiation perpetuation inflammation. Moreover, clinical animal model promising potential therapies for patients. In this review, we present an up-to-date overview focus on roles regulating functional subsets. Furthermore, discuss highlight its contribution development Based preclinical evidence, novel biomarkers disorders.

Язык: Английский

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

Life Sciences, Год журнала: 2023, Номер 336, С. 122322 - 122322

Опубликована: Дек. 1, 2023

Язык: Английский

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A Transcriptome Analysis of mRNAs and Long Non-Coding RNAs in Patients with Parkinson’s Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1535 - 1535

Опубликована: Янв. 28, 2022

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The number of cases PD expected to double by 2030, representing a heavy burden on healthcare system. Clinical symptoms include progressive loss dopaminergic neurons in substantia nigra midbrain, which leads striatal dopamine deficiency and, subsequently, causes motor dysfunction. Certainly, study transcriptome various RNAs plays crucial role this disease. In fact, aim was evaluate cohort subjects with compared control cohort. particular we focused mRNAs and long non-coding (lncRNA), using Illumina NextSeq 550 DX System. Differential expression analysis revealed 716 transcripts padj ≤ 0.05; among these, 630 were mRNA (coding protein), lncRNA, MT_tRNA. Ingenuity pathway (IPA, Qiagen) used perform functional analysis. highest statistically significant pathways were: IL-15 signaling, B cell receptor systemic lupus erythematosus signaling pathway, communication between innate adaptive immune cells, melatonin degradation II. Our findings further reinforce important roles mitochondria lncRNA parallel, support concept inverse comorbidity some cancers.

Язык: Английский

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The Spectrum of Extraglandular Manifestations in Primary Sjögren’s Syndrome

Journal of Personalized Medicine, Год журнала: 2023, Номер 13(6), С. 961 - 961

Опубликована: Июнь 7, 2023

Extraglandular manifestations (EGMs) in primary Sjogren’s syndrome (pSS) represent the clinical expression of systemic involvement this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees dysfunction. The existing gaps knowledge complex domain extraglandular extension pSS need to overcome order increase diagnostic accuracy pSS. timely identification EGMs, as early from subclinical stages, facilitated using highly specific biomarkers, thus preventing decompensated disease and severe complications. To date, there is no general consensus on criteria for range pSS, which associates important underdiagnosing subsequent undertreatment progression dysfunction these patients. This review article presents most recent basic science research conducted investigate pathogenic mechanisms leading In addition, it current treatment recommendations trends future therapeutic strategies based personalized treatment, well latest field prognostic biomarkers

Язык: Английский

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Early diagnosis and treatment for Sjögren's syndrome: current challenges, redefined disease stages and future prospects

Journal of Autoimmunity, Год журнала: 2020, Номер 117, С. 102590 - 102590

Опубликована: Дек. 11, 2020

Язык: Английский

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Integrated Bioinformatics and Validation Reveal Potential Biomarkers Associated With Progression of Primary Sjögren’s Syndrome

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Июль 23, 2021

Background Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease of the exocrine glands characterized by specific pathological features. Previous studies have pointed out that salivary from pSS patients express unique profile cytokines, adhesion molecules, and chemokines compared to those healthy controls. However, there limited evidence supporting utility individual markers for different stages pSS. This study aimed explore potential biomarkers associated with progression analyze associations between key genes immune cells. Methods We combined our own RNA sequencing data datasets NCBI Gene Expression Omnibus (GEO) database identify differentially expressed (DEGs) via bioinformatics analysis. Salivary gland biopsies were collected 14 patients, 6 non-pSS Histochemical staining transmission electron micrographs (TEM) performed macroscopically microscopically characterize morphological features labial in stages. Then, we quantitative PCR validate hub genes. Finally, analyzed correlations selected cells using CIBERSORT algorithm. Results identified twenty-eight DEGs upregulated These mainly involved immune-related pathways infection-related pathways. According minor glands, severe interlobular periductal lymphocytic infiltrates, acinar atrophy collagen interstitium, nuclear shrinkage, microscopic organelle swelling observed progression. Hub based on above DEGs, including MS4A1, CD19, TCL1A, CCL19, CXCL9, CD3G, CD3D, as verified RT-PCR. these was correlated T follicular helper cells, memory B M1 macrophages. Conclusion Using transcriptome analysis clinical data, seven value evaluating severity.

Язык: Английский

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Knockdown of RSAD2 attenuates B cell hyperactivity in patients with primary Sjögren’s syndrome (pSS) via suppressing NF-κb signaling pathway

Molecular and Cellular Biochemistry, Год журнала: 2021, Номер 476(5), С. 2029 - 2037

Опубликована: Янв. 29, 2021

Язык: Английский

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Lysosome-associated membrane protein 3 misexpression in salivary glands induces a Sjögren’s syndrome-like phenotype in mice

Annals of the Rheumatic Diseases, Год журнала: 2021, Номер 80(8), С. 1031 - 1039

Опубликована: Март 3, 2021

Sjögren's syndrome (SS) is an autoimmune sialadenitis with unknown aetiology. Although extensive research implicated abnormal immune response associated lymphocytes, initiating event mediated by salivary gland epithelial cell (SGEC) abnormalities causing activation poorly characterised. Transcriptome studies have suggested alternations in lysosomal function are SS, but a cause and effect linkage has not been established. In this study, we demonstrated that altered lysosome activity SGECs expression of lysosome-associated membrane protein 3 (LAMP3) can initiate autoantibody production dysfunction similar to SS.Retroductal cannulation the submandibular glands adeno-associated virus serotype 2 vector encoding LAMP3 was used establish model system. Pilocarpine-stimulated flow presence autoantibodies were assessed at several time points post-cannulation. Salivary from mice evaluated using RNAseq histologically.Following expression, saliva significantly decreased serum anti-Ro/SSA La/SSB antibodies could be detected treated mice. Mechanistically, increased apoptosis related secretion. Analysis data transduced SGECs, cellular changes chemoattract cells into glands. Immune activated via toll-like receptors damage-associated molecular patterns released LAMP3-expressing SGECs.These results show critical role for trafficking development SS causal relationship between misexpression SS.

Язык: Английский

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Dysregulated long non-coding RNA in Sjögren’s disease impacts both interferon and adaptive immune responses

RMD Open, Год журнала: 2022, Номер 8(2), С. e002672 - e002672

Опубликована: Ноя. 1, 2022

Objective Sjögren’s disease (SjD) is an autoimmune characterised by inflammatory destruction of exocrine glands. Patients with autoantibodies to Ro/SSA (SjD Ro+ ) exhibit more severe disease. Long non-coding RNAs (lncRNAs) are a functionally diverse class non-protein-coding whose role in pathology has not been well characterised. Methods Whole blood RNA-sequencing (RNA-seq) was performed on SjD cases (n=23 negative Ro− ); n=27 positive and healthy controls (HCs; n=27). Bioinformatics pathway analyses differentially expressed (DE) transcripts (log 2 fold change ≥2 or ≤0.5; p adj <0.05) were used predict lncRNA function. LINC01871 RNA-seq HSB-2 cells CRISPR-targeted deletion ( −/ − vitro stimulation assays. Results revealed autoantibody-specific transcription profiles disproportionate downregulation DE relative HCs. Sixteen lncRNAs exhibited correlated expression the interferon (IFN)-regulated gene, RSAD2 , (r≥0.65 ≤−0.6); four antisense IFN-regulated immune cell lines. upregulated all cases. implicated roles cytotoxic function, differentiation IFNγ induction. induced myeloid line regulated calcineurin/NFAT T receptor (TCR) signalling primary human cells. Conclusion influences many genes growth factors, inducible, calcineurin TCR ligand engagement. Altered may influence dysregulated pathways SjD.

Язык: Английский

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Integration of multi-omics analysis reveals metabolic alterations of B lymphocytes in systemic lupus erythematosus

Clinical Immunology, Год журнала: 2024, Номер 264, С. 110243 - 110243

Опубликована: Май 10, 2024

To link changes in the B-cell transcriptome from systemic lupus erythematosus (SLE) patients with those their macroenvironment, including cellular and fluidic components.

Язык: Английский

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