Project description:Genome wide DNA methylation profiling of human labial salivary gland (LSG) biopsy samples obtained from 28 female members of the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry. The Illumina HumanMethylation450 BeadChip platform was used to obtain DNA methylation profiles across more than 450,000 highly informative CpG sites. Samples included 15 non-case glands, and 13 glands from patients with Sjögren's Syndrome.
Project description:The study aims to investigate the relevance of NKp30 receptor in the salivary glands inflammation of Sjogren’s syndrome patients in comparison to sicca patients (control group) analysing the transcriptomic profile of salivary gland tissues.
Project description:The present study was aimed to identify aberrantly expressed lncRNAs involved in the progression of SjS and explore their potential functions. Labial salivary gland of 4 SjS patients and 4 healthy controls was collected. LncRNA expression profile in labial salivary gland was analyzed by LncRNA microarray.
Project description:Differential gene expression in the salivary gland during development and onset of xerostomia in Sjögren’s syndrome-like disease of the C57BL/6.NOD-Aec1Aec2 mouse. Recently, we reported the development of the C57BL/6.NOD-Aec1Aec2 mouse that carries two genetic intervals derived from the NOD mouse capable of conferring Sjögren’s syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. In an attempt to define the molecular bases underlying onset of stomatitis sicca (xerostomia) in this C57BL/6.NOD-Aec1Aec2 mouse model, we have carried out a study utilizing microarray technology.
Project description:While all salivary glands (SGs) can be involved in primary Sjögren’s syndrome (pSS), their respective role in pathogenesis remains unclear. To assess immunopathway activation in paired parotid and labial gland tissue from biopsy-positive and biopsy-negative pSS and non-SS sicca patients, paraffin-embedded, paired parotid and labial salivary gland tissue and peripheral blood mononuclear cells were obtained from 39 pSS and 20 non-SS sicca patients. The patients were subdivided based on fulfillment of ACR-EULAR criteria and histopathology and the samples were analyzed for differentially expressed genes (DEGs). The principal component analysis of SG gene expression could only separate biopsy-positive pSS from non-SS sicca patients. However, when comparing the transcriptome of biopsy-positive pSS and biopsy-negative non-SS sicca patients, 1235 and 624 DEGs (FDR<-1 or >1) were identified for parotid and labial glands, respectively. The number of DEGs between biopsy negative pSS and non-SS sicca patients was scarce. The overall, transcript expression levels correlated strongly between parotid and labial glands (R2=0.86, p‐value<0.0001). Gene signatures present in both glands of biopsy‐positive pSS patients included IFN‐α signaling, IL-12/IL-18 signaling, CD3/CD28 T-cell activation, CD40 signaling in B-cells, DN2 B-cells, and FcRL4+ B-cells. Signature scores varied considerably amongst pSS patients. In conclusion, the transcriptomes of paired major and minor SGs in pSS were overall comparable, although significant inter-individual heterogeneity in immunopathway activation existed. The SG transcriptome of biopsy-negative pSS was indistinguishable from non-SS sicca patients. The different patterns of SG immunopathway activation in pSS argue for personalized treatment approaches.
Project description:While all salivary glands (SGs) can be involved in primary Sjögren’s syndrome (pSS), their respective role in pathogenesis remains unclear. To assess immunopathway activation in paired parotid and labial gland tissue from biopsy-positive and biopsy-negative pSS and non-SS sicca patients, paraffin-embedded, paired parotid and labial salivary gland tissue and peripheral blood mononuclear cells were obtained from 39 pSS and 20 non-SS sicca patients. The patients were subdivided based on fulfillment of ACR-EULAR criteria and histopathology and the samples were analyzed for differentially expressed genes (DEGs). The principal component analysis of SG gene expression could only separate biopsy-positive pSS from non-SS sicca patients. However, when comparing the transcriptome of biopsy-positive pSS and biopsy-negative non-SS sicca patients, 1235 and 624 DEGs (FDR<-1 or >1) were identified for parotid and labial glands, respectively. The number of DEGs between biopsy negative pSS and non-SS sicca patients was scarce. The overall, transcript expression levels correlated strongly between parotid and labial glands (R2=0.86, p‐value<0.0001). Gene signatures present in both glands of biopsy‐positive pSS patients included IFN‐α signaling, IL-12/IL-18 signaling, CD3/CD28 T-cell activation, CD40 signaling in B-cells, DN2 B-cells, and FcRL4+ B-cells. Signature scores varied considerably amongst pSS patients. In conclusion, the transcriptomes of paired major and minor SGs in pSS were overall comparable, although significant inter-individual heterogeneity in immunopathway activation existed. The SG transcriptome of biopsy-negative pSS was indistinguishable from non-SS sicca patients. The different patterns of SG immunopathway activation in pSS argue for personalized treatment approaches.
Project description:Salivary glands that produce and secret saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we established long-term murine salivary gland organoids from 3 major salivary glands, including parotid gland (PG), submandibular gland (SMG), and sublingual gland (SLG). Murine salivary gland organoids expressed gland-specific genes and proteins of acinar, myoepithelial, and duct cells. Organoids were maintained in growth media (named GEM) and further underwent differentiation in differentiation media (named DAM). Our study will provide an experimental platform for the exploration of mechanisms involvled in tissue regeneration, development, or several salivary gland diseases.
Project description:ObjectiveSjögren's syndrome (SS) is a complex multisystem autoimmune disease that results in progressive destruction of the exocrine glands. The purpose of this study was to characterize epigenetic changes in affected gland tissue and describe the relationship of these changes to known inflammatory processes.MethodsA genome-wide DNA methylation study was performed on human labial salivary gland (LSG) biopsy samples obtained from 28 female members of the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry. Gland tissue was methylotyped using the Illumina HumanMethylation450 BeadChip platform, followed by rigorous probe-filtering and data-normalization procedures.ResultsA genome-wide case-control study of 26 of the 28 subjects revealed 7,820 differentially methylated positions (DMPs) associated with disease status, including 5,699 hypomethylated and 2,121 hypermethylated DMPs. Further analysis identified 57 genes that were enriched for DMPs in their respective promoters; many are involved in immune response, including 2 previously established SS genetic risk loci. Bioinformatics analysis highlighted an extended region of hypomethylation surrounding PSMB8 and TAP1, consistent with an increased frequency of antigen-presenting cells in LSG tissue from the SS cases. Transcription factor motif enrichment analysis revealed the specific nature of the genome-wide methylation differences, demonstrating colocalization of SS-associated DMPs with stress- and immune response-related motifs.ConclusionOur findings underscore the utility of CpG methylotyping as an independent probe of active disease processes in SS, offering unique insights into the composition of disease-relevant tissue. Methylation profiling implicated several genes and pathways previously thought to be involved in disease-related processes, as well as a number of new candidates.