TL1A promotes microglial inflammatory response via DR3-NF-κB signaling to mediate the progression of postoperative cognitive dysfunction

Abstract

Aim To investigate the mechanism by which tumor necrosis factor ligand-related molecule 1 A (TL1A) promotes the progression of postoperative cognitive dysfunction (POCD). Methods A POCD mouse model was established by splenectomy. Cognitive and behavioral abilities of mice were assessed using the Morris water maze, open field test, and novel object recognition test. Microglial activation and inflammatory cytokine levels were measured. Activation of the DR3-NF-κB signaling pathway was examined. The mechanism of TL1A was investigated using DR3-specific knockout mouse models and NF-κB inhibitors. Primary microglia were cultured in vitro to study the effect of TL1A on microglial inflammatory activation. Results TL1A promoted the progression of cognitive dysfunction in POCD mice, activated microglia, and exacerbated the inflammatory response. In DR3-specific knockout mice, the effect of TL1A was attenuated, and similarly, NF-κB inhibitors could also antagonize the action of TL1A. In vitro studies demonstrated that TL1A promoted the expression of inflammatory cytokines in microglia. Conclusion TL1A contributes to the progression of postoperative cognitive dysfunction in mice by promoting microglial activation. TL1A enhances microglial inflammatory response through activation of the DR3-NF-κB signaling pathway.

The authors' abstract, as published at the source. International Immunopharmacology, 2026 · DOI ↗