Rescue of hepatic fibrosis by pathogen molecular-reprogrammed macrophages with stable pro-resolution and strong chemotaxis capacity
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ABSTRACT: Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. However, the phenotypic heterogeneity of macrophages is a major barrier to successful clinical translation. Herein, we established a macrophage stably expressing a pivotal cytokine from T. gondii, a parasite that infects approximately two billion people, to ameliorate liver fibrosis. T. gondii macrophage migration inhibitory factor-reprogrammed macrophage (TgMIF-Mφ) promoted the polarization of classical activation of macrophages (M1) through the ERK/HMGB1/NF-κB pathway. Infusion of TgMIF-Mφ effectively ameliorated liver fibrosis by modulating immune microenvironment and promoting fibrinolysis. Remarkably, RNA-sequencing analysis and experiments in vivo demonstrated that TgMIF-Mφ exhibits higher chemotaxis potential and lower grade of inflammation than typical M1 macrophages induced by LPS/IFN-γ. Our study identifies TgMIF as a potential immune cell reprogramming agent for cytotherapy in experimental liver fibrosis, which sheds new light on the usage of ancient parasite-derived immunomodulators as potential therapeutic strategies for human diseases.
ORGANISM(S): Mus musculus
PROVIDER: GSE197639 | GEO | 2024/02/20
REPOSITORIES: GEO
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