ArticleJournal of Crohn's & colitis2020
Lymphocyte Activation Gene (LAG)-3 Is Associated With Mucosal Inflammation and Disease Activity in Ulcerative Colitis.
Article in Journal of Crohn's & colitis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Depletion of LAG-3Clinical pharmacology and therapeutics · 2021Trial
- Article
- The roles and heterogeneity of CD8International journal of molecular medicine · 2026Review
- Lymphocyte activation gene 3 in autoimmune disease: from molecular mechanisms to clinical applications.Frontiers in immunology · 2026Review
- Immunometabolic Contributions of Atopobiaceae Family Members in Human Papillomavirus Infection, Cervical Dysplasia, and Cancer.The Journal of infectious diseases · 2025Article
- Article
- LAG3 limits regulatory T cell proliferation in α-synuclein gut-to-brain transmission model.Journal of neuroinflammation · 2025Article
- Exploring new frontiers in LAG-3 biology and therapeutics.Trends in pharmacological sciences · 2025Review
- Differential Disease Behavior of Immune-Mediated Colitis Among Different Types of Immune Checkpoint Inhibition.Targeted oncology · 2025Article
- Exhausted Lag-3+ CD4+ T cells are increased in pediatric Inflammatory Bowel Disease.Clinical and experimental immunology · 2025Article
- Investigating the molecular mechanisms associated with ulcerative colitis through the application of single-cell combined spatial transcriptome sequencing.Frontiers in immunology · 2025Article
- Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.Molecular therapy. Methods & clinical development · 2024Article
- Unlocking therapeutic potential: Targeting lymphocyte activation Gene-3 (LAG-3) with fibrinogen-like protein 1 (FGL1) in systemic lupus erythematosus.Journal of translational autoimmunity · 2024Review
- LAG-3 transcriptomic expression correlates linearly with other checkpoints, but not with clinical outcomes.American journal of cancer research · 2024Article
- A machine learning approach toward automating spatial identification of LAG3+/CD3+ cells in ulcerative colitis.Scientific reports · 2023Article
- From bench to bedside: targeting lymphocyte activation gene 3 as a therapeutic strategy for autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Upregulation of LAG3 modulates the immune imbalance of CD4+ T-cell subsets and exacerbates disease progression in patients with alveolar echinococcosis and a mouse model.PLoS pathogens · 2023Article
- Clinicopathological significance and prognostic role of LAG3 + tumor-infiltrating lymphocytes in colorectal cancer; relationship with sidedness.Cancer cell international · 2023Article
- Beyond FOXP3: a 20-year journey unravelling human regulatory T-cell heterogeneity.Frontiers in immunology · 2023Review
- Biology-inspired data-driven quality control for scientific discovery in single-cell transcriptomics.Genome biology · 2022Article
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsLymphocyte activation gene [LAG]-3 is an immune checkpoint and its expression identifies recently activated lymphocytes that may contribute to inflammation. We investigated the role of LAG-3 by analysing its expression and function in immune cells from blood and tissue of patients with ulcerative colitis [UC].
methodsThe phenotypic properties of LAG-3+ T cells were determined by flow cytometry, qRT-PCR and single-cell RNA-sequencing. LAG-3+ cells were quantified and correlated with disease activity. The functional effects of LAG-3+ cells were tested using a depleting anti-LAG-3 monoclonal antibody [mAb] in a mixed lymphocyte reaction [MLR].
resultsLAG-3+ cells in the blood were negligible. LAG-3+ lymphocytes were markedly increased in inflamed mucosal tissue and both frequencies of LAG-3+ T cells and transcript levels of LAG3 correlated with endoscopic severity. LAG-3 expression was predominantly on effector memory T cells, and single-cell RNA-sequencing revealed LAG3 expression in activated and cytokine-producing T cell subsets. Foxp3+CD25hi Tregs also expressed LAG-3, although most mucosal Tregs were LAG-3-. Mucosal LAG-3+ cells produced mainly interferon γ [IFNγ] and interleukin-17A. LAG-3+ cell numbers decreased in patients who responded to biologics, and remained elevated in non-responders. Treatment with a depleting anti-LAG-3 mAb led to a reduction in proliferation and IFNγ production in an MLR.
conclusionsLAG-3+ cells are increased in the inflamed mucosa, predominantly on effector memory T cells with an activated phenotype and their cell numbers positively correlate with disease activity. Depleting LAG-3 eliminates activated proliferating T cells, and hence LAG-3 could be a therapeutic target in UC.
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