Folate receptor beta drives NLRP3 inflammasome activation and pyroptosis in macrophages independent of folate binding - PubMed
4 hours ago
- #macrophage activation
- #NLRP3 inflammasome
- #FRβ
- Folate receptor beta (FRβ) is a novel regulator of NLRP3 inflammasome activation and pyroptosis in human THP-1 macrophages, independent of folate binding.
- Loss of FOLR2 (encoding FRβ) impairs caspase-1 activation, gasdermin D cleavage, and IL-1β release in response to NLRP3 stimuli, without affecting pro-IL-1β induction.
- FRβ deficiency leads to broad transcriptional repression, increased CpG hypermethylation, and reduced expression of genes involved in inflammasome signaling and ion transport.
- Mechanistically, FRβ promotes NLRP3 activation by regulating potassium efflux, gene transcription, and DNA methylation in a folate-independent manner.
- These findings position FRβ as a potential modulator of macrophage-driven inflammation in host defense, autoimmunity, and tissue-specific immune responses.