Cited by 1,000Cell death mechanisms and regulationNF-κB Signaling PathwaysCytokine Signaling Pathways and Interactions

Regulation of tumour necrosis factor signalling: live or let die

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Brenner, Dirk, Blaser, Heiko, Mak, Tak W.·2015·Nature Reviews Immunology

Abstract

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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  • Biological outcome of TNFR1 signaling spans from cell survival and activation to multiple subroutines of RCD, depending on cell-intrinsic and cell-extrinsic factors.

    “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].”

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  1. A comprehensive review about the TNFSF and TNFRSF, TNF signalling in cell survival and death, and clinical and therapeutic implications of targeting TNF signalling.

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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
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
  • Health Sciences › Medicine › Oncology › 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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