An NF-kB/TNF-alpha signalling feedback loop acts to coordinate tissue regeneration and macrophage behaviour in zebrafish.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40461478.
- Also identified by DOI 10.1038/s41536-025-00414-1 and PMC identifier 12134371.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Inflammatory cells are crucial regulators of infection and regeneration that actively migrate to affected tissues. NF-kB and TNF-alpha (TNFα) are master regulators of immune signalling, but their importance for immune cell migration is much less well understood. We have therefore investigated how NF-kB and TNFα regulate both macrophage function and behaviour in vivo using a zebrafish model of tissue repair. We show that NF-kB activity differentially regulates TNFα activity through Tnf receptors 1a and 1b to control macrophage responses to injury. Loss of NF-kB in macrophages results in elevated TNFα expression and results in more directional migration. Impaired NF-kB activity in macrophages perturbs tissue regeneration, causes increased proliferation, altered pro- and anti-inflammatory gene expression and delays fin regeneration. We identify a crucial role for NF-kB modulation of TNFα signaling to regulate macrophage responses to tissue injury, which are necessary for effective fin regeneration.