Abstract
BackgroundRecent studies have proven the existence of distinct monocyte subsets, which play a significant role in the development of some rheumatic diseases such as systemic lupus erythematosus (SLE). This study was performed to define the changes of monocyte subsets in patients with Sjögren’s Syndrome (SjS).MethodsSingle cell RNA-sequencing (scRNA-seq) data of monocytes from SjS patients and controls were analyzed. The transcriptomic changes in monocyte subsets between SjS and controls were identified and potential key functional pathways involved in SjS development were also explored.ResultsA total of 11 monocyte subsets were identified in the scRNA-seq analyses of monocytes. A new monocyte subset characterized by higher expression of VNN2 (GPI-80) and S100A12 (Monocyte cluster 3) was identified, and it was increased in SjS patients. Compared with controls, almost all monocyte subsets from SjS patients had increased expression of TNFSF10 (TRAIL). Moreover, interferon (IFN)-related and neutrophil activation-associated pathways were main up-regulated pathways in the monocytes of SjS patients.ConclusionThis study uncovered the abnormal changes in monocyte subsets and their transcriptomic changes in SjS patients, and identified TNFSF10 high/+ monocytes as a potential key player in SjS pathogenesis and a promising target for SjS treatment.
Highlights
Sjögren’s Syndrome (SjS) is a complex rheumatic disease characterized by the infiltration of immune cells into exocrine glands such as salivary glands, and effective targeted therapies for SjS are still lacking [1, 2]
A new monocyte subset characterized by higher expression of VNN2 (GPI-80) and S100A12 (Monocyte cluster 3, C3) was identified, and it was increased in SjS patients (Figures 1B, C)
Through scRNA-seq transcriptome analyses, a number of significant differentially expressed genes (DEGs) in monocyte subsets of SjS patients were identified, such as TMEM176B, TMEM176A, HLA-DRB5, FOS, TXNIP, ARPC1B, GRN, FGL2, SAMHD1, CEBPD, CTSZ, HLA-DQB1, SNX17, TNFSF10, WASF2, ATP5A1, ZFP36L2 and CORO1A (Figures 2A, B). Some of those significant DEGs above such as HLA-DRB5 and TNFSF10 have been proved to be key players in the pathogeneses of many autoimmune or rheumatic diseases. Enrichment analyses of those significant DEGs identified neutrophil activationassociated pathways and IFN-related pathways as the main upregulated pathways in the monocytes of SjS patients, (Figures 2C, D) suggesting that those pathways had the vital roles in SjS pathogenesis
Summary
SjS is a complex rheumatic disease characterized by the infiltration of immune cells into exocrine glands such as salivary glands, and effective targeted therapies for SjS are still lacking [1, 2]. Current studies suggest that some factors such as disease susceptibility genes, immune abnormalities, and viral infections are synergistically involved in its pathogenesis of SjS [3–5]. Among those factors, abnormal immune factors such as B cell hyperactivity have been considered as key players in SjS pathogenesis and potential targets for SjS treatment [6, 7]. Recent studies using scRNA-seq have demonstrated the existence of distinct monocyte subsets and they have crucial roles in the development of some rheumatic diseases such as SLE [14, 15]. Recent studies have proven the existence of distinct monocyte subsets, which play a significant role in the development of some rheumatic diseases such as systemic lupus erythematosus (SLE). This study was performed to define the changes of monocyte subsets in patients with Sjögren’s Syndrome (SjS)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
