Adoptive transfer of VSIG4+ macrophages interrupts the CCL2-CCR2 inflammatory amplification loop to mitigate acetaminophen-induced acute liver injury in murine and human organoid models

作者：Biao Duan, Jun Chen, Guan Liu, Jiacheng Lin, Shiyu Yang, Xiaoni Kong, Weifang Rong, Weifeng Tan · 发表于：Figshare · 年份：2026 · DOI：10.6084/m9.figshare.c.8606282.v1 · 研究领域：Medicine、Immunology、Cancer research、Pathology、Biology

Abstract Background Acute liver injury (ALI) can rapidly progress to life-threatening acute liver failure. Liver transplantation remains the only definitive treatment, despite critical donor shortages. Macrophage-based therapies have shown promise in ALI but face challenges related to subset imprecision and limited humanized validation. VSIG4 is generally considered a marker of Kupffer cells; however, it is also expressed in monocyte-derived macrophages (MoMFs), and its role remains unclear during ALI. Methods By integrating single-cell RNA sequencing (scRNA-seq) data from human and mouse liver tissues with clinical ALI tissue samples, we elucidated the dynamic changes in VSIG4+ macrophages (VSIG4+ Mφ) within the liver. We developed a reversible immunomagnetic nanoparticle system for the non-destructive isolation of viable VSIG4+ Mφ. The therapeutic efficacy and potential mechanisms of VSIG4+ Mφ were evaluated through tissue and molecular-level analyses in an acetaminophen (APAP)-induced ALI mouse model, as well as in a newly established vascularized human liver organoid ALI and monocyte chemotaxis model. Results scRNA-seq revealed a previously underrecognized subpopulation of VSIG4+ MoMFs, which increases following ALI, while the number of resident VSIG4+ Kupffer cells decreases significantly. Clinical ALI tissue samples also confirmed the presence of CCR2+VSIG4+ cells in the livers of patients with ALI. In the APAP-induced ALI animal model, adoptive transfer of isolated VSI...