biostudies-literatureGao JNational Natural Science Foundation of China (National Science Foundation of China)2077https://www.ebi.ac.uk/biostudies/studies/S-EPMC12949000biostudies-literatureUnknown17(1)Chimeric antigen receptor macrophages (CAR-Ms) therapy has shown great promise in liver fibrosis, however limited anti-inflammatory capacity of CAR-Ms in the fibrotic foci compromises their anti-fibrotic potency. We here report tripartite motif containing 13 (TRIM13) engineered CAR-Ms for effectively manipulating the anti-inflammatory phenotype of CAR-Ms, augmenting their anti-fibrosis efficacy. Specifically, our efferocytosis-sparked lipid nanoparticles (ESLNPs) efficiently engineered fibrosis-associated macrophages to anti-inflammatory CAR-Ms by co-delivering mRNA encoding TRIM13 and anti-fibroblast activation protein (FAP) CAR respectively. Our data demonstrated these reprogrammed CAR-Ms exhibited a sustained anti-inflammatory phenotype via blocking the mitochondrial DNA (mtDNA)-STING pNature communicationsTRIM13 in situ engineering boosts anti-inflammatory capacity of CAR-Ms for liver fibrosis therapy.PMC1294900082350125，82425056，82173763Li CDong XShao LBo LHan MTang CFu ZGao JChen CZhao XLi NYang ZLi YLi TJiang XDai KZhao KSong YfalseTRIM13 in situ engineering boosts anti-inflammatory capacity of CAR-Ms for liver fibrosis therapy.Chimeric antigen receptor macrophages (CAR-Ms) therapy has shown great promise in liver fibrosis, however limited anti-inflammatory capacity of CAR-Ms in the fibrotic foci compromises their anti-fibrotic potency. We here report tripartite motif containing 13 (TRIM13) engineered CAR-Ms for effectively manipulating the anti-inflammatory phenotype of CAR-Ms, augmenting their anti-fibrosis efficacy. Specifically, our efferocytosis-sparked lipid nanoparticles (ESLNPs) efficiently engineered fibrosis-associated macrophages to anti-inflammatory CAR-Ms by co-delivering mRNA encoding TRIM13 and anti-fibroblast activation protein (FAP) CAR respectively. Our data demonstrated these reprogrammed CAR-Ms exhibited a sustained anti-inflammatory phenotype via blocking the mitochondrial DNA (mtDNA)-STING p2026-01-01T00:00:00Z2026 Feb2026-07-16T23:15:31.524Z2026-07-12T03:11:10.024ZS-EPMC129490004176065810.1038/s41467-026-69858-3