ArticleProceedings of the National Academy of Sciences of the United States of America2014
Essential role for autophagy during invariant NKT cell development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 109 citations in OpenAlex.
- Mitophagy and Immune Infiltration in Primary Sjögren's Disease: Insights from Bioinformatics Analysis.International journal of molecular sciences · 2026Article
- Revisiting T cells: Innate actions and emerging links to innate memory response.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Metabolic control of innate-like T cells.Nature reviews. Immunology · 2026Review
- NKT cells-a generalist in disease treatment and a new key to unlock immunotherapy.Immunotherapy · 2025Review
- Autophagy in tumor immune escape and immunotherapy.Molecular cancer · 2025Review
- PRR enhances anti-tumor immunity and suppresses colitis by promoting the development and survival of naive T and iNKT cells.Frontiers in immunology · 2025Article
- Multi-omics approach to dissect the significance of lipid metabolism in helper T cell subset.Frontiers in immunology · 2025Review
- Multi-dimensional roles of sodium-glucose cotransporter 2 inhibitors: beyond hypoglycemic and cardiorenal protection.Frontiers in endocrinology · 2025Review
- Gpx4 Regulates Invariant NKT Cell Homeostasis and Function by Preventing Lipid Peroxidation and Ferroptosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Article
- Targeted Mevalonate Pathway and Autophagy in Antitumor Immunotherapy.Current cancer drug targets · 2024Review
- Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies.Molecular cancer · 2023Review
- Invariant natural killer T cells in lung diseases.Experimental & molecular medicine · 2023Review
- Discovery of fecal microbial signatures in patients with ankylosing spondylitis.Archives of rheumatology · 2023Article
- Cullin 3-Mediated Regulation of Intracellular Iron Homeostasis Promotes Thymic Invariant NKT Cell Maturation.ImmunoHorizons · 2023Article
- Impaired thymic iNKT cell differentiation at early precursor stage in murine haploidentical bone marrow transplantation with GvHD.Frontiers in immunology · 2023Article
- Autophagy and Its Lineage-Specific Roles in the Hematopoietic System.Oxidative medicine and cellular longevity · 2023Review
- NKT cells adopt a glutamine-addicted phenotype to regulate their homeostasis and function.Cell reports · 2022Article
- Autophagy in Cancer Immunotherapy.Cells · 2022Review
- A guide to membrane atg8ylation and autophagy with reflections on immunity.The Journal of cell biology · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 2 countries.
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Abstract
Autophagy is an evolutionarily conserved cellular homeostatic pathway essential for development, immunity, and cell death. Although autophagy modulates MHC antigen presentation, it remains unclear whether autophagy defects impact on CD1d lipid loading and presentation to invariant natural killer T (iNKT) cells and on iNKT cell differentiation in the thymus. Furthermore, it remains unclear whether iNKT and conventional T cells have similar autophagy requirements for differentiation, survival, and/or activation. We report that, in mice with a conditional deletion of the essential autophagy gene Atg7 in the T-cell compartment (CD4 Cre-Atg7(-/-)), thymic iNKT cell development--unlike conventional T-cell development--is blocked at an early stage and mature iNKT cells are absent in peripheral lymphoid organs. The defect is not due to altered loading of intracellular iNKT cell agonists; rather, it is T-cell-intrinsic, resulting in enhanced susceptibility of iNKT cells to apoptosis. We show that autophagy increases during iNKT cell thymic differentiation and that it developmentally regulates mitochondrial content through mitophagy in the thymus of mice and humans. Autophagy defects result in the intracellular accumulation of mitochondrial superoxide species and subsequent apoptotic cell death. Although autophagy-deficient conventional T cells develop normally, they show impaired peripheral survival, particularly memory CD8(+) T cells. Because iNKT cells, unlike conventional T cells, differentiate into memory cells while in the thymus, our results highlight a unique autophagy-dependent metabolic regulation of adaptive and innate T cells, which is required for transition to a quiescent state after population expansion.
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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.