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Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage\u2010based immunotherapy using macrophages stably expressing a pivotal cytokine from\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    , a parasite that infects \u2248 2 billion people is developed. It is found that\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    macrophage migration inhibitory factor\u2010transgenic macrophage (M\u03c6\n                    <jats:italic>\n                      <jats:sup>tgmif<\/jats:sup>\n                    <\/jats:italic>\n                    ) shows stable fibrinolysis and strong chemotactic capacity. M\u03c6\n                    <jats:italic>\n                      <jats:sup>tgmif<\/jats:sup>\n                    <\/jats:italic>\n                    effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    macrophages via paracrine CCL2 and polarizing them into the restorative Ly6C\n                    <jats:sup>lo<\/jats:sup>\n                    macrophage through the secretion of CX3CL1. Remarkably, M\u03c6\n                    <jats:italic>\n                      <jats:sup>tgmif<\/jats:sup>\n                    <\/jats:italic>\n                    exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS\/IFN\u2010\u03b3\u2010treated macrophages, making macrophage\u2010based immune therapy more efficient and safer. Mechanistically,\n                    <jats:italic>Tg<\/jats:italic>\n                    MIF promotes CCL2 expression by activating the ERK\/HMGB1\/NF\u2010\u03baB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202308750","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T01:21:25Z","timestamp":1705886485000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Protozoan\u2010Derived Cytokine\u2010Transgenic Macrophages Reverse Hepatic Fibrosis"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-5402","authenticated-orcid":false,"given":"Ying","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Research Center for Infectious Diseases School of Basic Medical Sciences Anhui Medical University  Hefei 230032 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