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Regulation of tumour necrosis factor signalling: live or let die
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Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that has important roles in mammalian immunity and cellular homeostasis. Deregulation of TNF receptor (TNFR) signalling is associated with many inflammatory disorders, including various types of arthritis and inflammatory bowel disease, and targeting TNF has been an effective therapeutic strategy in these diseases. This Review focuses on the recent advances that have been made in understanding TNFR signalling and the consequences of its deregulation for cellular survival, apoptosis and regulated necrosis. We discuss how TNF-induced survival signals are distinguished from those that lead to cell death. Finally, we provide a brief overview of the role of TNF in inflammatory and autoimmune diseases, and we discuss up-to-date and future treatment strategies for these disorders.
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“As mentioned above, the biological outcome of TNFR1 signaling spans from cell survival and activation (i.e., cytokine secretion) to multiple subroutines of RCD, depending on a variety of cell-intrinsic (e.g., expression levels of the proteins involved in the process) and cell-extrinsic (e.g., intensity and duration of TNF stimulation) factors [283].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [283]
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Metadata
- Authors
- Brenner, D., Blaser, H., & Mak, T. W.
- Affiliations
- Luxembourg Institute of Health (LU)
- University Health Network (CA)
- Corresponding author
- Brenner, Dirk
- Venue
- Nature Reviews Immunology
- Published
- 2015-05-26
- Volume
- 15
- Issue
- 6
- Pages
- 362-374
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W1572664742
- Cited by
- 998
- References
- 182
- Citations by year
- 2026: 52 · 2025: 88 · 2024: 81 · 2023: 97 · 2022: 100 · 2021: 112 · 2020: 107 · 2019: 94 · 2018: 96 · 2017: 84 · 2016: 75 · 2015: 11
- FWCI
- 8.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
- Funders
- Fonds National de la Recherche Luxembourg
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- TNF-α, cell survival, apoptosis, regulated necrosis, inflammatory diseases, autoimmune disease, arthritis, inflammatory bowel disease, inflammatory cytokines
- MeSH terms
- Animals, Autoimmune Diseases, Cell Communication, Homeostasis, Humans, Inflammation, Tumor Necrosis Factor-alpha, NF-kappa B, Apoptosis, Membrane Microdomains, Ubiquitination, Activation, Metabolic
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