ArticlePloS one2014
T-cell autophagy deficiency increases mortality and suppresses immune responses after sepsis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 58 citations in OpenAlex.
- The impact of ulinastatin on lymphocyte apoptosis and autophagy in sepsis patients.Scientific reports · 2024Trial
- Fluids in sepsis.BJA education · 2026Review
- T-cell dysfunction and death in sepsis: a mechanistic review.Frontiers in immunology · 2026Review
- Immunosenescence in Sepsis: Molecular Mechanisms and Potential Therapeutic Targets.Aging and disease · 2025Review
- Sepsis-induced immunosuppression: mechanisms, biomarkers and immunotherapy.Frontiers in immunology · 2025Review
- Human Umbilical Cord-Derived Mesenchymal Stem Cells-Exosomes-Delivered miR-375 Targets HDAC4 to Promote Autophagy and Suppress T Cell Apoptosis in Sepsis-Associated Acute Kidney Injury.Applied biochemistry and biotechnology · 2024Article
- Autophagy and autophagic cell death in sepsis: friend or foe?Journal of intensive care · 2024Review
- Lymphopenia in sepsis: a narrative review.Critical care (London, England) · 2024Review
- A novel anoikis-related gene signature predicts prognosis in patients with sepsis and reveals immune infiltration.Scientific reports · 2024Article
- Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions.Frontiers in immunology · 2024Review
- Review
- Identification of autophagy-related genes and immune cell infiltration characteristics in sepsis via bioinformatic analysis.Journal of thoracic disease · 2023Article
- Myeloid autophagy genes protect mice against fatal TNF- and LPS-induced cytokine storm syndromes.Autophagy · 2023Article
- Advances in the Study of Immunosuppressive Mechanisms in Sepsis.Journal of inflammation research · 2023Review
- Myocardial injury: where inflammation and autophagy meet.Burns & trauma · 2023Review
- USP9x promotes CD8Acta biochimica et biophysica Sinica · 2022Article
- T cell dysregulation in inflammatory diseases in ICU.Intensive care medicine experimental · 2022Review
- mTOR deletion ameliorates CD4 + T cell apoptosis during sepsis by improving autophagosome-lysosome fusion.Apoptosis : an international journal on programmed cell death · 2022Article
- The "Self-Sacrifice" of ImmuneCells in Sepsis.Frontiers in immunology · 2022Review
- The Role of Autophagy in the Function of CD4Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough the role of autophagy in sepsis has been characterized in several organs, its role in the adaptive immune system remains to be ascertained. This study aimed to investigate the role of autophagy in sepsis-induced T cell apoptosis and immunosuppression, using knockout mice with T cell specific deletion of autophagy essential gene Atg7. METHODS AND
resultsSepsis was induced in a cecal ligation and puncture (CLP) model, with T-cell-specific Atg7-knockout mice compared to control mice. Autophagic vacuoles examined by electron microscopy were decreased in the spleen after CLP. Autophagy proteins LC3-II and ATG7, and autophagosomes and autolysosomes stained by Cyto-ID Green and acridine orange were decreased in CD4+ and CD8+ splenocytes at 18 h and 24 h after CLP. This decrease in autophagy was associated with increased apoptosis of CD4+ and CD8+ after CLP. Moreover, mice lacking Atg7 in T lymphocytes showed an increase in sepsis-induced mortality, T cell apoptosis and loss of CD4+ and CD8+ T cells, in comparison to control mice. This was accompanied by suppressed cytokine production of Th1/Th2/Th17 by CD4+ T cells, reduced phagocytosis in macrophages and decreased bacterial clearance in the spleen after sepsis.
conclusionThese results indicated that sepsis led to down-regulation of autophagy in T lymphocytes, which may result in enhanced apoptosis induction and decreased survival in sepsis. Autophagy may therefore play a protective role against sepsis-induced T lymphocyte apoptosis and immunosuppression.
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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.