ArticleAnnals of the rheumatic diseases2019
Phosphatidylinositol 3-kinase delta pathway: a novel therapeutic target for Sjögren's syndrome.
Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome.JCI insight · 2022Trial
- Akt Signaling Pathway Is Activated in the Minor Salivary Glands of Patients with Primary Sjögren's Syndrome.International journal of molecular sciences · 2021Trial
- Review
- Molecular Insights into Oral Manifestations in Sjögren's Disease.International journal of molecular sciences · 2026Review
- mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Review
- A comprehensive review of Sjögren's syndrome: Classification criteria, risk factors, and signaling pathways.Heliyon · 2024Review
- Environmental pollutants and phosphoinositide signaling in autoimmunity.Journal of hazardous materials · 2024Review
- PI3Kδ Pathway Dysregulation and Unique Features of Its Inhibition by Leniolisib in Activated PI3Kδ Syndrome and Beyond.The journal of allergy and clinical immunology. In practice · 2024Article
- Investigative biological therapies for primary Sjögren's syndrome.Archives of medical science : AMS · 2024Article
- Outline of Salivary Gland Pathogenesis of Sjögren's Syndrome and Current Therapeutic Approaches.International journal of molecular sciences · 2023Review
- B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma.International journal of molecular sciences · 2023Article
- The Role of the Akt Signaling Pathway in Sjögren's Syndrome.Mediterranean journal of rheumatology · 2023Article
- GITRL impairs the immunosuppressive function of MDSCs via PTEN-mediated signaling pathway in experimental Sjögren syndrome.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Cenerimod, a selective S1PArthritis research & therapy · 2021Article
- Targeted Therapy for Primary Sjögren's Syndrome: Where are We Now?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Review
- Biologic therapy in Sjögren's syndrome.Clinical rheumatology · 2021Review
- Immune complexome analysis reveals the presence of immune complexes and identifies disease-specific immune complex antigens in saliva samples from patients with Sjögren's syndrome.Clinical and experimental immunology · 2021Article
- Innate Immunity and Biological Therapies for the Treatment of Sjögren's Syndrome.International journal of molecular sciences · 2020Review
- Autophagy occurs in lymphocytes infiltrating Sjögren's syndrome minor salivary glands and correlates with histological severity of salivary gland lesions.Arthritis research & therapy · 2020Article
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundThe phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration and has been successfully targeted in B-cell malignancies. Primary Sjögren's syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration and B-cell hyperactivation which results in systemic manifestations, autoantibody production and loss of glandular function. Given the central role of B cells in pSS pathogenesis, we investigated PI3Kδ pathway activation in pSS and the functional consequences of blocking PI3Kδ in a murine model of focal sialoadenitis that mimics some features of pSS. METHODS AND
resultsTarget validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands. In vivo blockade of PI3Kδ activity with seletalisib, a PI3Kδ-selective inhibitor, in a murine model of focal sialoadenitis decreased accumulation of lymphocytes and plasma cells within the glands of treated mice in the prophylactic and therapeutic regimes. Additionally, production of lymphoid chemokines and cytokines associated with ectopic lymphoneogenesis and, remarkably, saliva flow and autoantibody production, were significantly affected by treatment with seletalisib.
conclusionThese data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition.
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