ArticleArthritis and rheumatism2013
Interleukin-7 enhances the Th1 response to promote the development of Sjögren's syndrome-like autoimmune exocrinopathy in mice.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 67 citations in OpenAlex.
- Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.British journal of clinical pharmacology · 2019Trial
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- Altered characteristics of regulatory T cells in target tissues of Sjögren's syndrome in murine models.Molecular immunology · 2024Article
- Endogenous IL-22 contributes to the pathogenesis of salivary gland dysfunction in the non-obese diabetic model of Sjögren's syndrome.Molecular immunology · 2024Article
- The role of cytokines from salivary gland epithelial cells in the immunopathology of Sjögren's syndrome.Frontiers in immunology · 2024Review
- Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren's syndrome.Frontiers in immunology · 2024Review
- Inhibition of NLRP3 inflammasome activity by MCC950 leads to exacerbation of Sjӧgren's syndrome pathologies in non-obese diabetic mice.Immunology · 2023Article
- SOXC Transcription Factors as Diagnostic Biomarkers and Therapeutic Targets for Arthritis.International journal of molecular sciences · 2023Review
- JAK/STAT Pathway Targeting in Primary Sjögren Syndrome.Rheumatology and immunology research · 2022Review
- Review
- Plasmacytoid dendritic cells promote the pathogenesis of Sjögren's syndrome.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Low Dose Interleukin-2 Ameliorates Sjögren's Syndrome in a Murine Model.Frontiers in medicine · 2022Article
- Profiling and Characterization of Localized Cytokine Response in Congenital Cleft Affected Lip Tissue.Life (Basel, Switzerland) · 2021Article
- Epithelial-immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis.Nature reviews. Rheumatology · 2021Review
- Blockade of IL-7 signaling suppresses inflammatory responses and reverses alopecia areata in C3H/HeJ mice.Science advances · 2021Article
- Immunobiology of T Cells in Sjögren's Syndrome.Clinical reviews in allergy & immunology · 2021Review
- Transcriptome Analysis of CCR9+ T Helper Cells From Primary Sjögren's Syndrome Patients Identifies CCL5 as a Novel Effector Molecule.Frontiers in immunology · 2021Article
- T Cells Subsets in the Immunopathology and Treatment of Sjogren's Syndrome.Biomolecules · 2020Review
- Contributions of Major Cell Populations to Sjögren's Syndrome.Journal of clinical medicine · 2020Review
- Recent Advances in Mouse Models of Sjögren's Syndrome.Frontiers in immunology · 2020Review
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4 authors at 1 institution in 1 country.
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Abstract
objectiveAlthough elevated interleukin-7 (IL-7) levels have been reported in patients with primary Sjögren's syndrome (SS), the role of IL-7 in this disease remains unclear. We undertook this study to characterize the previously unexplored role of IL-7 in the development and onset of primary SS using the C57BL/6.NOD-Aec1Aec2 (B6.NOD-Aec) mouse model, which recapitulates human primary SS.
methodsFor gain-of-function studies, recombinant IL-7 or control phosphate buffered saline was injected intraperitoneally (IP) into 12-week-old B6.NOD-Aec mice for 8 weeks. For loss-of-function studies, anti-IL-7 receptor α-chain (anti-IL-7Rα) antibody or its isotype control IgG was administered IP into 16-week-old B6.NOD-Aec mice. Salivary flow measurement, histologic and flow cytometric analysis of salivary glands, and serum antinuclear antibody assay were performed to assess various disease parameters.
resultsAdministration of exogenous IL-7 accelerated the development of primary SS, whereas blockade of IL-7Rα signaling almost completely abolished the development of primary SS, based on salivary gland inflammation and apoptosis, autoantibody production, and secretory dysfunction. IL-7 positively regulated interferon-γ (IFNγ)-producing Th1 and CD8+ T cells in the salivary glands without affecting IL-17. Moreover, IL-7 enhanced the expression of CXCR3 ligands in a T cell- and IFNγ-dependent manner. Accordingly, IFNγ induced a human salivary gland epithelial cell line to produce CXCR3 ligands. IL-7 also increased the level of tumor necrosis factor α, another Th1-associated cytokine that can facilitate tissue destruction and inflammation.
conclusionIL-7 plays a pivotal pathogenic role in SS, which is underpinned by an enhanced Th1 response and IFNγ/CXCR3 ligand-mediated lymphocyte infiltration of target organs. These results suggest that targeting the IL-7 pathway may be a potential future strategy for preventing and treating SS.
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