ArticleThe Journal of clinical investigation2022
Lysosomal exocytosis of HSP70 stimulates monocytic BMP6 expression in Sjögren's syndrome.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Composition and regulation of the immune microenvironment of salivary gland in Sjögren's syndrome.Frontiers in immunology · 2022Pooled it
- Single-cell analysis highlights the role of CD4Biology direct · 2026Article
- Multi-omics Mendelian randomization prioritizes BMP6 as a candidate therapeutic target in intervertebral disc degeneration.Journal of orthopaedic surgery and research · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
- Bone Morphogenetic Protein 6 Attenuates Psoriasis Pathogenesis by Suppressing Th17 Cell Differentiation.Inflammation · 2026Article
- ACSL5 programs fatty acid metabolism and mitochondrial fitness to sustain pathogenic T cells and exacerbate Sjögren's syndrome.International journal of biological sciences · 2026Article
- Lipid Metabolism: An Emerging Player in Sjögren's Syndrome.Clinical reviews in allergy & immunology · 2025Review
- Identification and Validation of Pyroptosis-Associated Gene Signature in Primary Sjögren's Syndrome.Mediators of inflammation · 2025Article
- A protracted war against cancer drug resistance.Cancer cell international · 2024Review
- Update on the pathophysiology and treatment of primary Sjögren syndrome.Nature reviews. Rheumatology · 2024Review
- Exorbital Lacrimal Gland Ablation and Regrafting Induce Inflammation but Not Regeneration or Dry Eye.International journal of molecular sciences · 2024Article
- Primary Sjögren's syndrome: new perspectives on salivary gland epithelial cells.European journal of medical research · 2024Review
- Amplified Type I Interferon Response in Sjögren's Disease via Ectopic Toll-Like Receptor 7 Expression in Salivary Gland Epithelial Cells Induced by Lysosome-Associated Membrane Protein 3.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- A model approach to show that monocytes can enter microporous β-TCP ceramics.BMC biotechnology · 2024Article
- BMP6 inhibits gastric cancer growth and predicts good prognosis.Journal of gastrointestinal oncology · 2024Article
- Article
- Lysosome-Associated Membrane Protein 3 Induces Lysosome-Dependent Cell Death by Impairing Autophagic Caspase 8 Degradation in the Salivary Glands of Individuals With Sjögren's Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Regulatory T cells alleviate myelin loss and cognitive dysfunction by regulating neuroinflammation and microglial pyroptosis via TLR4/MyD88/NF-κB pathway in LPC-induced demyelination.Journal of neuroinflammation · 2023Article
- LAMP3 transfer via extracellular particles induces apoptosis in Sjögren's disease.Scientific reports · 2023Article
- Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sjögren's disease.PloS one · 2023Article
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 4 countries.
Funding
Abstract
BMP6 is a central cytokine in the induction of Sjögren's syndrome-associated (SS-associated) secretory hypofunction. However, the upstream initiation leading to the production of this cytokine in SS is unknown. In this study, RNA ISH on salivary gland sections taken from patients with SS indicated monocytic lineage cells as a cellular source of BMP6. RNA-Seq data on human salivary glands suggested that TLR4 signaling was an upstream regulator of BMP6, which was confirmed by in vitro cell assays and single-cell transcriptomics of human PBMCs. Further investigation showed that HSP70 was an endogenous natural TLR4 ligand that stimulated BMP6 expression in SS. Release of HSP70 from epithelial cells could be triggered by overexpression of lysosome-associated membrane protein 3 (LAMP3), a protein also associated with SS in several transcriptome studies. In vitro studies supported the idea that HSP70 was released as a result of lysosomal exocytosis initiated by LAMP3 expression, and reverse transcription PCR on RNA from minor salivary glands of patients with SS confirmed a positive correlation between BMP6 and LAMP3 expression. BMP6 expression could be experimentally induced in mice by overexpression of LAMP3, which developed an SS-like phenotype. The newly identified LAMP3/HSP70/BMP6 axis provided an etiological model for SS gland dysfunction and autoimmunity.
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Registered trials
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.