ArticleProceedings of the National Academy of Sciences of the United States of America2019
Autophagy genes in myeloid cells counteract IFNγ-induced TNF-mediated cell death and fatal TNF-induced shock.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. 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, 44 citations in OpenAlex.
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- Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages.Biomedicines · 2024Article
- Effector-mediated subversion of proteasome activator (PA)28αβ enhances host defense against Legionella pneumophila under inflammatory and oxidative stress conditions.PLoS pathogens · 2023Article
- Myeloid autophagy genes protect mice against fatal TNF- and LPS-induced cytokine storm syndromes.Autophagy · 2023Article
- Atg8ylation as a host-protective mechanism againstFrontiers in tuberculosis · 2023Article
- The association between type 2 diabetes and pulmonary cavitation revealed among IGRA-positive tuberculosis patients.Frontiers in medicine · 2023Article
- A guide to membrane atg8ylation and autophagy with reflections on immunity.The Journal of cell biology · 2022Article
- Regulation of PGC1α Downstream of the Insulin Signaling Pathway Plays a Role in the Hepatic Proteotoxicity of Mutant α1-Antitrypsin Deficiency Variant Z.Gastroenterology · 2022Article
- Identification of a novel autophagy-related prognostic signature and small molecule drugs for glioblastoma by bioinformatics.BMC medical genomics · 2022Article
- IKKβ Alleviates Neuron Injury in Alzheimer's Disease via Regulating Autophagy and RIPK1-Mediated Necroptosis.Molecular neurobiology · 2022Article
- Tumor immunology CRISPR screening: present, past, and future.Trends in cancer · 2022Review
- The (re)discovery of tumor-intrinsic determinants of immune sensitivity by functional genetic screens.Immuno-oncology technology · 2021Review
- Article
- TNF-α synergises with IFN-γ to induce caspase-8-JAK1/2-STAT1-dependent death of intestinal epithelial cells.Cell death & disease · 2021Article
- OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection.Nature communications · 2021Article
- Minimized combinatorial CRISPR screens identify genetic interactions in autophagy.Nucleic acids research · 2021Article
- Article
- These Are the Genes You're Looking For: Finding Host Resistance Genes.Trends in microbiology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Host inflammatory responses must be tightly regulated to ensure effective immunity while limiting tissue injury. IFN gamma (IFNγ) primes macrophages to mount robust inflammatory responses. However, IFNγ also induces cell death, and the pathways that regulate IFNγ-induced cell death are incompletely understood. Using genome-wide CRISPR/Cas9 screening, we identified autophagy genes as central mediators of myeloid cell survival during the IFNγ response. Hypersensitivity of autophagy gene-deficient cells to IFNγ was mediated by tumor necrosis factor (TNF) signaling via receptor interacting protein kinase 1 (RIPK1)- and caspase 8-mediated cell death. Mice with myeloid cell-specific autophagy gene deficiency exhibited marked hypersensitivity to fatal systemic TNF administration. This increased mortality in myeloid autophagy gene-deficient mice required the IFNγ receptor, and mortality was completely reversed by pharmacologic inhibition of RIPK1 kinase activity. These findings provide insight into the mechanism of IFNγ-induced cell death via TNF, demonstrate a critical function of autophagy genes in promoting cell viability in the presence of inflammatory cytokines, and implicate this cell survival function in protection against mortality during the systemic inflammatory response.
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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.