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

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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

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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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Authors: Brenner, D., Blaser, H., & Mak, T. W.
Affiliations: Luxembourg Institute of Health (LU)
University Health Network (CA)
Corresponding author: Brenner, Dirk
ORCID: Brenner, Dirk
Mak, Tak W.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2015-05-26
Volume: 15
Issue: 6
Pages: 362-374
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri3834
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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