{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:12:48Z","timestamp":1785208368745,"version":"3.55.0"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171810"],"award-info":[{"award-number":["82171810"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pyruvate dehydrogenase kinase 2 (PDK2) regulates glucose metabolism; however, its role in liver injury development is unknown. Therefore, this study aimed to explore the effects of PDK2 on liver injury using a concanavalin A (Con A)\u2010induced acute liver injury mouse model. To understand the mechanisms by which PDK2 affects liver injury pathogenesis, network pharmacology analysis was performed to pinpoint the potential target genes and signaling pathways involved. Con A was used to induce acute liver injury in mice. Thereafter,\n                    <jats:italic>PDK2<\/jats:italic>\n                    differential expression levels in the liver tissue of normal and liver injury mice were analyzed, and the effects of PDK2 inhibition on Con A\u2010induced liver damage were assessed through biochemical analysis and observation of hepatic histopathological changes. Enzyme\u2010linked immunosorbent assay, quantitative polymerase chain reaction, flow cytometry, and western blotting were used to explore the possible mechanisms by which PDK2 affects liver injury. PDK2 was involved in liver injury progression, and pharmacological inhibition of PDK2 notably increased mouse survival, decreased serum alanine transaminase and aspartate aminotransferase levels, attenuated hepatic histopathological damage and apoptosis, and inhibited pro\u2010inflammatory cytokine secretion and the activation of the mitogen\u2010activated protein kinase\/nuclear factor kappa B (MAPK\/NF\u2010\u03baB) signaling pathway. Pharmacological inhibition of PDK2 markedly alleviated hepatic oxidative stress and elevated myeloid\u2010derived suppressor cells (MDSCs) in the livers of acute liver injury mice. Overall, inhibiting PDK2 ameliorates Con A\u2010induced acute liver injury by enhancing MDSCs accumulation and suppressing oxidative stress, the MAPK\/NF\u2010\u03baB signaling pathway, and inflammation. These findings identify PDK2 as a promising therapeutic target for immune\u2010mediated hepatitis.\n                  <\/jats:p>","DOI":"10.1111\/imm.70053","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T01:35:28Z","timestamp":1760578528000},"page":"339-354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of Pyruvate Dehydrogenase Kinase 2 Alleviates Concanavalin A\u2010Induced Acute Liver Injury by Regulating Myeloid\u2010Derived Suppressor Cells"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8248-0284","authenticated-orcid":false,"given":"Chunxia","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Immunology and Molecular Medicine, Basic Medical School Jining Medical University  Jining People's Republic of 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