ArticleProceedings of the National Academy of Sciences of the United States of America2015
Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 41 citations in OpenAlex.
- CD5L is a potential negative regulator of chondrocyte apoptosis in osteoarthritis.Osteoarthritis and cartilage open · 2026Article
- High glucose-induced mitophagy accelerates premature aging of T cells in patients with rheumatoid arthritis.Clinical rheumatology · 2026Article
- Splicing-aware scRNA-Seq resolution reveals execution-ready programs in effector Tregs.PLoS computational biology · 2025Article
- Dysfunctional glycolysis-UCP2-fatty acid oxidation promotes CTLA4Molecular medicine (Cambridge, Mass.) · 2025Article
- Transcriptomic Analysis of Blood Collagen-Induced Arthritis Mice Exposed to 0.1 THz Reveals Inhibition of Genes and Pathways Involved in Rheumatoid Arthritis.International journal of molecular sciences · 2024Article
- CRISPR-GEM: A Novel Machine Learning Model for CRISPR Genetic Target Discovery and Evaluation.ACS synthetic biology · 2024Article
- CRISPR-GEM: A Novel Machine Learning Model for CRISPR Genetic Target Discovery and Evaluation.bioRxiv : the preprint server for biology · 2024Article
- The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis.Nature communications · 2024Article
- Identification of key proteins in early-onset Alzheimer's disease based on WGCNA.Frontiers in aging neuroscience · 2024Article
- The Chromatin Landscape of Pathogenic Transcriptional Cell States in Rheumatoid Arthritis.bioRxiv : the preprint server for biology · 2023Article
- The Study of the Association of Polymorphisms inInternational journal of molecular sciences · 2023Article
- Dawn-to-dusk dry fasting induces anti-atherosclerotic, anti-inflammatory, and anti-tumorigenic proteome in peripheral blood mononuclear cells in subjects with metabolic syndrome.Metabolism open · 2022Article
- Cyclosporine A Modulates LSP1 Protein Levels in Human B Cells to Attenuate B Cell Migration at Low OLife (Basel, Switzerland) · 2022Article
- Deficiency of leukocyte-specific protein 1 (LSP1) alleviates asthmatic inflammation in a mouse model.Respiratory research · 2022Article
- Single-cell eQTL analysis of activated T cell subsets reveals activation and cell type-dependent effects of disease-risk variants.Science immunology · 2022Article
- Intrahepatic activated leukocyte cell adhesion molecule induces CD6Frontiers in immunology · 2022Article
- LSP1-myosin1e bimolecular complex regulates focal adhesion dynamics and cell migration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8Science translational medicine · 2021Article
- Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies.Frontiers in immunology · 2021Article
- Regulation of tumor growth by leukocyte-specific protein 1 in T cells.Journal for immunotherapy of cancer · 2020Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in Lsp1-deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T-cell-dependent chronic inflammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA.
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