Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren’s syndrome

Inamo, Jun; Suzuki, Katsuya; Takeshita, Masaru; Kassai, Yoshiaki; Takiguchi, Maiko; Kurisu, Rina; Okuzono, Yuumi; Tasaki, Shinya; Yoshimura, Akihiko; Takeuchi, Tsutomu

doi:10.1186/s13075-020-02248-2

Cited by 30 publications

(22 citation statements)

References 43 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A pilot study by Dolcino et al (34) identified 199 differentially expressed lnRNAs, such as LINC00657 and LINC00511, in peripheral blood mononuclear cells (PBMCs), suggesting that lncRNAs might be involved in the pathogenesis of pSS. Inamo et al (35) demonstrated that the LINC00487 lncRNA was significantly up-regulated in B-cells and associated with the dysregulation of B-cells in pSS. In addition, the PVT1 lncRNA was found to be involved in glycolytic metabolism reprogramming and proliferation upon activation of CD4+ Tcells (36).…”

Section: Discussionmentioning

confidence: 99%

Predicted Disease-Specific Immune Infiltration Patterns Decode the Potential Mechanisms of Long Non-Coding RNAs in Primary Sjogren’s Syndrome

et al. 2021

View full text Add to dashboard Cite

Primary Sjogren’s syndrome (pSS) is a chronic progressive autoimmune disease with clinical phenotypic “Sicca symptoms”. In some cases, the diagnosis of pSS is delayed by 6–7 years due to the inefficient differential diagnosis of pSS and non-SS “Sicca”. This study aimed to investigate the difference between these two diseases, and in particular, their immunopathogenesis. Based on their gene expression profiles, we systematically defined for the first time the predicted disease-specific immune infiltration pattern of patients with pSS differentiated from normal donors and patients with non-SS “Sicca”. We found that it was characterized by the aberrant abundance and interaction of tissue-infiltrated immune cells, such as a notable shift in the subpopulation of six immune cells and the perturbed abundance of nine subpopulations, such as CD4+ memory, CD8+ T-cells and gamma delta T-cells. In addition, we identified essential genes, particularly long non-coding RNAs (lncRNAs), as the potential mechanisms linked to this predicted pattern reprogramming. Fourteen lncRNAs were identified as the potential regulators associated with the pSS-specific immune infiltration pattern in a synergistic manner, among which the CTA-250D10.23 lncRNA was highly relevant to chemokine signaling pathways. In conclusion, aberrant predicted disease-specific immune infiltration patterns and relevant genes revealed the immunopathogenesis of pSS and provided some clues for the immunotherapy by targeting specific immune cells and genes.

show abstract

Section: Discussionmentioning

confidence: 99%

Predicted Disease-Specific Immune Infiltration Patterns Decode the Potential Mechanisms of Long Non-Coding RNAs in Primary Sjogren’s Syndrome

et al. 2021

View full text Add to dashboard Cite

show abstract

“…[2][3][4][5] Transcriptome studies of minor salivary gland biopsies and peripheral blood mononuclear cells identified additional IFN signature genes that were increased in patients with SS. [6][7][8][9] Many cellular proteins are reported to be regulated by IFN expression include those associated with lysosomal function. Lysosome-associated membrane protein 3 (LAMP3) is a membrane glycoprotein predominantly localised in lysosomes that is reported to be induced by IFN.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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

show abstract

“…Moreover, the gene expression profiles of more than 200 PBMC samples of pSS have been investigated, and WGCNA analysis was applied to explore the gene-network signature and potential functions of hub genes based on Gene Expression Omnibus (GEO) public database (Yao et al, 2019). Recently, Inamo et al (2020) also identified LINC00487 and SOX4 as key genes associated with the dysregulation of B cells in pSS patients using WGCNA algorithm. These studies provided a convincing possibility that WGCNA can be effectively applied to identify hub genes as biomarkers for the early detection of pSS and facilitate a deep understanding of its pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Sequencing Reveals Potential Roles of ICOS in Primary Sjögren’s Syndrome

Luo

Liao

Zhang

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by exocrine gland damage and extraglandular involvements. To identify potential biomarkers for the early detection of pSS and to further investigate the potential roles of the biomarkers in the progression of pSS, our previous RNA sequencing data and four microarray data of salivary glands (SGs) were combined for integrative transcriptome analysis between pSS and non-pSS. Differential gene expression analysis, gene co-expression network analysis, and pathway analysis were conducted to detect hub genes, which were subsequently investigated in peripheral blood mononuclear cell (PBMC) and plasma. Correlation analysis, single-gene Gene Set Enrichment Analysis, and receiver operating characteristic (ROC) curve were applied to investigate the potential function of the hub genes and their classification capacity for pSS. A total of 51 common up-regulated genes were identified among different pSS cohorts. A key module was found to be the most closely linked to pSS, which was significantly associated with inflammation-related pathways. Seven overlapped hub genes (ICOS, SELL, CR2, BANK1, MS4A1, ZC3H12D, and CCR7) were identified, among which ICOS was demonstrated to be involved in most crucial immune pathways. ICOS was up-regulated not only in SGs but also in PBMC and plasma in pSS, and the expression of ICOS was closely associated with lymphocytic infiltration in SGs and disease activity of pSS patients. It showed a strong classification capacity with classic clinical index in SGs (ROC curve 0.9821) and significant distinct discrimination in PBMC (ROC curve 0.9107). These findings are expected to gain a further insight into the pathogenesis of pSS and provide a promising candidate for the early detection of pSS.

show abstract

Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren’s syndrome

Cited by 30 publications

References 43 publications

Predicted Disease-Specific Immune Infiltration Patterns Decode the Potential Mechanisms of Long Non-Coding RNAs in Primary Sjogren’s Syndrome

Predicted Disease-Specific Immune Infiltration Patterns Decode the Potential Mechanisms of Long Non-Coding RNAs in Primary Sjogren’s Syndrome

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

Transcriptome Sequencing Reveals Potential Roles of ICOS in Primary Sjögren’s Syndrome

Contact Info

Product

Resources

About