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Baricitinib is a selective Janus kinase (JAK) 1\/2 inhibitor that shows promise in autoimmune diseases such as rheumatoid arthritis. However, its efficacy in immune\u2010mediated liver injury has not been fully elucidated. In this study, we found that JAK2 inhibitors fedratinib and baricitinib significantly mitigated liver damage, as evidenced by reduced serum transaminase levels, diminished histopathological injury, and suppressed inflammatory responses in concanavalin A (ConA)\u2010induced liver injury, a classic animal model of immune\u2010mediated liver injury. Mechanistic studies revealed that baricitinib's protective effects were mediated through JAK2 inhibition in macrophages. Myeloid\u2010specific JAK2 knockout mice exhibited blunted activation of macrophages and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, conferring resistance to immune\u2010mediated liver injury induction. In\u00a0vitro, macrophages isolated from baricitinib\u2010treated or JAK2\u2010deficient mice displayed less mature and activated phenotypes as evidenced by lower expressions of major histocompatibility complex class II (MHC\u2010II), inflammatory marker Ly6C, inflammatory cytokine production, and higher phagocytic capacity, which subsequently resulted in lower levels of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation. These findings collectively underscore baricitinib's therapeutic potential in modulating immune responses and restoring hepatic homeostasis in immune\u2010mediated liver injury, positioning it as a promising therapeutic candidate for this challenging condition. Further clinical validation is warranted to translate these preclinical insights into patient care.\n                  <\/jats:p>","DOI":"10.1096\/fj.202504763rr","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T14:40:38Z","timestamp":1776264038000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting\n                    <scp>JAK2<\/scp>\n                    : Genetic and Pharmacological Inhibition Attenuates Immune\u2010Mediated Liver Injury by Suppressing Proinflammatory Macrophage"],"prefix":"10.1096","volume":"40","author":[{"given":"Xinlu","family":"Li","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Immunology, Department of Internal Medicine Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan Hubei 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