TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.
Journal
Nature reviews. Rheumatology
ISSN: 1759-4804
Titre abrégé: Nat Rev Rheumatol
Pays: United States
ID NLM: 101500080
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
accepted:
05
07
2023
medline:
24
8
2023
pubmed:
5
8
2023
entrez:
4
8
2023
Statut:
ppublish
Résumé
The cytokine TNF signals via two distinct receptors, TNF receptor 1 (TNFR1) and TNFR2, and is a central mediator of various immune-mediated diseases. Indeed, TNF-neutralizing biologic drugs have been in clinical use for the treatment of many inflammatory pathological conditions, including various rheumatic diseases, for decades. TNF has pleiotropic effects and can both promote and inhibit pro-inflammatory processes. The integrated net effect of TNF in vivo is a result of cytotoxic TNFR1 signalling and the stimulation of pro-inflammatory processes mediated by TNFR1 and TNFR2 and also TNFR2-mediated anti-inflammatory and tissue-protective activities. Inhibition of the beneficial activities of TNFR2 might explain why TNF-neutralizing drugs, although highly effective in some diseases, have limited benefit in the treatment of other TNF-associated pathological conditions (such as graft-versus-host disease) or even worsen the pathological condition (such as multiple sclerosis). Receptor-specific biologic drugs have the potential to tip the balance from TNFR1-mediated activities to TNFR2-mediated activities and enable the treatment of diseases that do not respond to current TNF inhibitors. Accordingly, a variety of reagents have been developed that either selectively inhibit TNFR1 or selectively activate TNFR2. Several of these reagents have shown promise in preclinical studies and are now in, or approaching, clinical trials.
Identifiants
pubmed: 37542139
doi: 10.1038/s41584-023-01002-7
pii: 10.1038/s41584-023-01002-7
doi:
Substances chimiques
Receptors, Tumor Necrosis Factor, Type II
0
Receptors, Tumor Necrosis Factor, Type I
0
Tumor Necrosis Factor-alpha
0
Cytokines
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
576-591Informations de copyright
© 2023. Springer Nature Limited.
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