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Signalling pathways of the TNF superfamily: a double-edged sword

Aggarwal, Bharat B.·2003·Nature Reviews Immunology

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Abstract

Two different tumour-necrosis factors (TNFs), first isolated in 1984, were found to be cytotoxic to tumour cells and to induce tumour regression in mice. Research during the past two decades has shown the existence of a superfamily of TNF proteins consisting of 19 members that signal through 29 receptors. These ligands, while regulating normal functions such as immune responses, haematopoiesis and morphogenesis, have also been implicated in tumorigenesis, transplant rejection, septic shock, viral replication, bone resorption, rheumatoid arthritis and diabetes; so indicating their role as 'double-edged swords'. These cytokines either induce cellular proliferation, survival, differentiation or apoptosis. Blockers of TNF have been approved for human use in treating TNF-linked autoimmune diseases in the United States and other countries.

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Authors: Aggarwal, B. B.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Aggarwal, Bharat B.
ORCID: Aggarwal, Bharat B.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2003-09
Volume: 3
Issue: 9
Pages: 745-756
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri1184
OpenAlex: W2095013915
Cited by: 2,793
References: 124
Citations by year: 2026: 74 · 2025: 107 · 2024: 82 · 2023: 121 · 2022: 125 · 2021: 114 · 2020: 132 · 2019: 113 · 2018: 114 · 2017: 130 · 2016: 108 · 2015: 142 · 2014: 128 · 2013: 116 · 2012: 159
FWCI: 9.77
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: TNF superfamily, TNF-α, TNF receptor, signaling pathways, carcinogenesis, graft rejection, septic shock, viral replication, bone resorption, rheumatoid arthritis, diabetes mellitus, apoptosis, TNF-alpha inhibitors, autoimmune disease, cytokines
MeSH terms: Animals, Autoimmune Diseases, Carrier Proteins, Humans, Ligands, Lymphotoxin-alpha, Membrane Proteins, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, Receptors, Tumor Necrosis Factor, Mice

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Signalling pathways of the TNF superfamily: a double-edged sword

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