ArticleAnnals of the rheumatic diseases2024
Inhibition of JAK-STAT pathway corrects salivary gland inflammation and interferon driven immune activation in Sjögren's disease.
Article in Annals of the rheumatic diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Insights into the pathogenesis of rheumatic and immune diseases from single-cell omics.Frontiers in immunology · 2026Pooled it
- JAK inhibitor tofacitinib alleviates secretory dysfunction and Th17/Treg imbalance in a Sjögren's disease murine model.Annals of medicine · 2026Article
- Managing Sjögren's Disease in Pediatric Patients.Paediatric drugs · 2026Review
- T Cell-Derived IFN-γ Activates Ferroptosis in Lacrimal Luminal Ductal Cells via JAK-STAT Signaling in Sjögren's Disease-Related Dry Eye.Investigative ophthalmology & visual science · 2026Article
- Mitochondrial RNA-Type I Interferon Axis in Sjögren's Disease: Molecular Mechanisms and Translational Implications.International journal of molecular sciences · 2026Review
- Agomelatine for Sjögren's syndrome: a study on its therapeutic effects and mechanisms.Inflammopharmacology · 2026Article
- Cytokine Networks and Clinical Heterogeneity in Sjögren's Disease: From Glandular Inflammation to Therapeutic Stratification.International journal of molecular sciences · 2026Review
- Molecular Insights into Oral Manifestations in Sjögren's Disease.International journal of molecular sciences · 2026Review
- An integrated single-cell and spatial proteotranscriptomics atlas of fibroblast-driven immunoregulation within the human adult oral cavity.Cell press blue · 2026Article
- A Mouthful of Genomic Data: Single-Cell Insights into Salivary Gland Biology and Disease.Biology · 2026Review
- Update on the Aetiopathogenesis of Sjögren Disease: From Interferon Signaling to Epithelial Dysfunction.Journal of clinical medicine · 2026Review
- NRIP1 disrupts ERα signal in Sjögren's disease via AQP5 suppression and MYC-driven salivary dysfunction.Experimental & molecular medicine · 2026Article
- IL-36 mediates immune activation in Sjögren's disease and may represent a novel biomarker of disease.Journal of leukocyte biology · 2026Article
- The power of genetics in decoding Sjögren's disease: current status and future development.Current opinion in immunology · 2026Review
- Sjögren's Disease-Associated Renal Tubular Acidosis: An Integrated Immuno-Tubular Model of Tubular Dysfunction.International journal of medical sciences · 2026Review
- Spatiotemporal orchestration of the salivary gland immune microenvironment in Sjögren's disease: a multidimensional framework of epithelial licensing, lymphoid neogenesis, and stromal remodeling.Frontiers in immunology · 2026Review
- IL-27: A Double-Edged Sword in Immune Regulation via JAK-STAT Orchestration.Journal of immunology research · 2026Review
- Janus kinase inhibitor use and incident dry eye disease in rheumatoid arthritis: a real-world cohort study.Frontiers in immunology · 2026Article
- Macrophage polarization in Sjögren's syndrome: from mechanisms to therapeutic translation.Frontiers in immunology · 2026Review
- Thrombotic thrombocytopenic purpura and macrophage activation syndrome secondary to Sjögren's syndrome: a case report.Frontiers in immunology · 2026Article
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25 authors at 1 institution in 1 country.
Funding
Abstract
objectivesInflammatory cytokines that signal through the Janus kinases-signal transducer and activator of transcription (JAK-STAT) pathway, especially interferons (IFNs), are implicated in Sjögren's disease (SjD). Although inhibition of JAKs is effective in other autoimmune diseases, a systematic investigation of IFN-JAK-STAT signalling and the effect of JAK inhibitor (JAKi) therapy in SjD-affected human tissues has not been fully investigated.
methodsHuman minor salivary glands (MSGs) and peripheral blood mononuclear cells (PBMCs) were investigated using bulk or single-cell (sc) RNA sequencing (RNAseq), immunofluorescence (IF) microscopy and flow cytometry. Ex vivo culture assays on PBMCs and primary salivary gland epithelial cell (pSGEC) lines were performed to model changes in target tissues before and after JAKi.
resultsRNAseq and IF showed activated JAK-STAT pathway in SjD MSGs. Elevated IFN-stimulated gene (ISGs) expression associated with clinical variables (eg, focus scores, anti-SSA positivity). scRNAseq of MSGs exhibited cell type-specific upregulation of JAK-STAT and ISGs; PBMCs showed similar trends, including markedly upregulated ISGs in monocytes. Ex vivo studies showed elevated basal pSTAT levels in SjD MSGs and PBMCs that were corrected with JAKi. SjD-derived pSGECs exhibited higher basal ISG expressions and exaggerated responses to IFN-β, which were normalised by JAKi without cytotoxicity.
conclusionsSjD 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, suggesting a putative viable therapy for SjD, targeting both glandular and extraglandular symptoms. Predicated on these data, a phase Ib/IIa randomised controlled trial to treat SjD with tofacitinib was initiated.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.