ArticleThe American journal of pathology2009
Critical roles of lysosomal acid lipase in T cell development and function.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 57 citations in OpenAlex.
- KRAS Signaling Inhibition Induces a Targetable Metabolic Dependency on Lipophagy-Dependent Fatty Acid Oxidation in Pancreatic Cancer.Cancer research · 2026Article
- Lysosomes in the immunometabolic reprogramming of immune cells in atherosclerosis.Nature reviews. Cardiology · 2025Review
- The role of lipophagy in liver cancer: mechanisms and targeted therapeutic interventions.Frontiers in cell and developmental biology · 2025Review
- Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.International journal of molecular sciences · 2024Article
- Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives.Molecular cancer · 2024Review
- BAP31 Knockout in Macrophages Affects CD4International journal of molecular sciences · 2023Article
- LAL deficiency induced myeloid-derived suppressor cells as targets and biomarkers for lung cancer.Journal for immunotherapy of cancer · 2023Article
- Lysosomal Acid Lipase Deficiency: Genetics, Screening, and Preclinical Study.International journal of molecular sciences · 2022Review
- Lysosomal acid lipase, CSF1R, and PD-L1 determine functions of CD11c+ myeloid-derived suppressor cells.JCI insight · 2022Article
- The role of lipid metabolism in shaping the expansion and the function of regulatory T cells.Clinical and experimental immunology · 2022Review
- The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders.Cell death & disease · 2022Review
- BATF Regulates T Regulatory Cell Functional Specification and Fitness of Triglyceride Metabolism in Restraining Allergic Responses.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Autophagy and organelle homeostasis in cancer.Developmental cell · 2021Review
- Lysosomal Acid Lipase Deficiency Controls T- and B-Regulatory Cell Homeostasis in the Lymph Nodes of Mice with Human Cancer Xenotransplants.The American journal of pathology · 2021Article
- T-Cell Metabolism in GraftFrontiers in immunology · 2021Review
- Recent Metabolic Advances for Preventing and Treating Acute and Chronic Graft Versus Host Disease.Frontiers in immunology · 2021Review
- Lysosomal Acid Lipase Is Required for Donor T Cells to Induce Graft-versus-Host Disease.Cell reports · 2020Article
- Review
- Lysosomal Acid Lipase Deficiency: Therapeutic Options.Drug design, development and therapy · 2020Review
- Pro-Survival Lipid Sphingosine-1-Phosphate Metabolically Programs T Cells to Limit Anti-tumor Activity.Cell reports · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Lysosomal acid lipase (LAL) cleaves cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in lysosomes. In LAL gene-knockout (lal(-/-)) mice, blockage of cholesteryl ester and triglyceride metabolism led to abnormal organization of the thymus and spleen, as well as neutral lipid accumulation in these organs. LAL deficiency impaired T cell development in the thymus. Peripheral T cells were reduced dramatically in lal(-/-) mice, due largely to increased apoptosis and decreased proliferation of lal(-/-) T cells in the thymus and peripheral compartments. These lal(-/-) T cells lost the ability to respond to T cell receptor stimulation, including reduced expression of cell surface receptor CD69, abolishment of T cell proliferation, and decreased expression of T lymphokines after stimulation by either anti-CD3 plus anti-CD28 or phorbol-12-myristate-13-acetate and ionomycin. Differentiation of Th1 and Th2 CD4(+) effector lymphocytes by T cell receptor stimulation was blocked in lal(-/-) mice. The ratio of CD4(+)CD25(+)FoxP3(+) Tregs to CD4(+) T cells was increased in lal(-/-) spleens. Bone marrow chimeras demonstrated retardation of T cell development and maturation in lal(-/-) mice due to defects in T cell precursors. Therefore, LAL, its downstream genes, and lipid mediators all play essential roles in development, homeostasis, and function of T cells. The altered development and function of lal(-/-) T cells contributes to disease formation in various organs during LAL deficiency.
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Registered trials
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