Sjögren's disease & overlap diseases
Inhibition of Janus kinases-signal transducer and activator of transcription (JAK-STAT) pathway corrects salivary gland inflammation and interferon driven immune activation in Sjögren's disease
Authors' conclusion
SjD patients' tissues exhibit increased expression of ISGs and activation of the JAK-STAT pathway in a cell type-dependent manner. JAKi normalises this aberrant signalling at the tissue level and in PBMCs
Study context
- Population
- Human minor salivary glands, peripheral blood mononuclear cells (PBMCs) and primary salivary gland epithelial cell lines from patients with Sjögren's disease (SjD)
- Comparison
- SjD vs control tissues; before vs after JAK inhibitor (JAKi) ex vivo
Methodological detailsbulk and single-cell RNA sequencing, immunofluorescence microscopy, flow cytometry, ex vivo culture assays
- Bulk and single-cell RNA sequencing
- Immunofluorescence microscopy
- Flow cytometry
- Ex vivo culture assays
Main finding
As reported in the abstract
- Activated JAK-STAT pathway in SjD minor salivary glands (RNA sequencing (RNAseq) and immunofluorescence (IF))
- Elevated ISG expression associated with clinical variables (eg, focus scores, anti-SSA positivity)
- Cell type-specific upregulation of JAK-STAT and ISGs in minor salivary glands (MSGs) (scRNAseq); similar trends in PBMCs, with markedly upregulated ISGs in monocytes
- Elevated basal pSTAT levels in SjD MSGs and PBMCs corrected with JAKi ex vivo
- SjD-derived pSGECs: higher basal ISG expression and exaggerated IFN-β responses, normalised by JAKi without cytotoxicity
Original publication
Inhibition of JAK-STAT pathway corrects salivary gland inflammation and interferon driven immune activation in Sjögren's disease. Ann Rheum Dis. Published 15 July 2024. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →