{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:12:53Z","timestamp":1778649173998,"version":"3.51.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Concanavalin A (ConA)-induced acute hepatitis is a widely used murine model for studying immune-mediated liver injury, characterized by T-cell activation and pro-inflammatory cytokine production. Mesenchymal stem cells (MSCs) have shown promise in mitigating liver injury through immunomodulation, but the precise cellular and molecular mechanisms remain unclear. This study leverages single-cell RNA sequencing (scRNA-seq) to elucidate the role of MSCs in reshaping the hepatic immune microenvironment during acute liver injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single-cell suspensions were isolated from liver tissues of ConA-induced acute hepatitis mice, with or without MSC treatment. ScRNA-seq libraries were generated using the 10\u00d7 Genomics platform, and data were processed using Seurat for quality control, clustering, and cell-type annotation. Trajectory and pseudotime analysis were performed using Monocle 3 to model differentiation pathways. Ligand-receptor interactions were analyzed using CellChat to identify active signaling pathways. Key findings were further assessed\n                      <jats:italic>in situ<\/jats:italic>\n                      by multiplex immunohistochemistry (mIHC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MSC administration markedly alleviated ConA-induced acute liver injury. scRNA-seq analysis showed that the global hepatic cellular landscape remained largely dominated by the acute inflammatory challenge, whereas MSC treatment was associated with selective remodeling of specific immune compartments. In particular, MSC treatment reduced the proportions of MDSCs, Tregs, NK cells, and proliferating CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, while increasing monocyte-derived macrophages (MoMFs). Subclustering and pseudotime analyses revealed heterogeneous MoMF states distributed along distinct transcriptional branches, including inflammatory and tissue-remodeling-associated programs. Combined with the compositional changes, these findings suggest selective remodeling of MoMF states following MSC treatment rather than uniform suppression of all macrophage subsets. Cell\u2013cell communication analysis further identified MoMFs as a major signaling hub, with complement-associated signaling emerging as a prominent communication module directed toward downstream MDSCs and NK cells. Consistently, mIHC showed increased CD206-associated macrophage staining and reduced CD86 signal in MSC-treated livers compared with ConA-treated livers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MSCs ameliorate acute immune-mediated liver injury in association with selective remodeling of the hepatic immune microenvironment, particularly within the MoMF compartment. These findings support a model in which MSC treatment is linked to altered macrophage-state composition and MoMF-centered complement-associated communication during injury resolution, providing insight into the innate immune mechanisms underlying MSC-mediated hepatoprotection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1809194","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:45:43Z","timestamp":1778647543000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mesenchymal stem cell alleviate concanavalin A-induced hepatitis via immune reprogramming and complement regulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Hanpeng","family":"Luo","sequence":"first","affiliation":[{"name":"Intervention and Cell Therapy Center, Peking University Shenzhen Hospital","place":["Shenzhen, Guangdong, 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