{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T19:50:37Z","timestamp":1782330637622,"version":"3.54.5"},"reference-count":97,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82222038"],"award-info":[{"award-number":["82222038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012397","name":"Army Medical University","doi-asserted-by":"publisher","award":["2023XQN49"],"award-info":[{"award-number":["2023XQN49"]}],"id":[{"id":"10.13039\/501100012397","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Chinese Journal of Traumatology"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.cjtee.2025.08.001","type":"journal-article","created":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T14:55:42Z","timestamp":1757170542000},"page":"157-166","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["TIM-3, a potential target for sepsis therapy"],"prefix":"10.1016","volume":"29","author":[{"given":"Shaowen","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xifeng","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengying","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huacai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anyong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9640-9083","authenticated-orcid":false,"given":"Ling","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cjtee.2025.08.001_bib1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1007\/s00134-017-4683-6","article-title":"Surviving Sepsis Campaign: international Guidelines for management of Sepsis and septic shock: 2016","volume":"43","author":"Rhodes","year":"2017","journal-title":"Intensive Care Med"},{"key":"10.1016\/j.cjtee.2025.08.001_bib2","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.3390\/jcm12093188","article-title":"2023 update on sepsis and septic shock in adult patients: management in the emergency department","volume":"12","author":"Guarino","year":"2023","journal-title":"J Clin Med"},{"key":"10.1016\/j.cjtee.2025.08.001_bib3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.cjtee.2025.08.001_bib4","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cjtee.2018.05.001","article-title":"Long-term quality of life after sepsis and predictors of quality of life in survivors with sepsis","volume":"21","author":"Su","year":"2018","journal-title":"Chin J Traumatol (Engl Ed)"},{"key":"10.1016\/j.cjtee.2025.08.001_bib5","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1186\/s13054-020-02950-2","article-title":"Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis","volume":"24","author":"Bauer","year":"2020","journal-title":"Crit Care"},{"key":"10.1016\/j.cjtee.2025.08.001_bib6","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.it.2021.06.001","article-title":"The 'cytokine storm': molecular mechanisms and therapeutic prospects","volume":"42","author":"Karki","year":"2021","journal-title":"Trends Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib7","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.ymthe.2021.12.013","article-title":"Tim-3 regulates sepsis-induced immunosuppression by inhibiting the NF-\u03baB signaling pathway in CD4 T cells","volume":"30","author":"Huang","year":"2022","journal-title":"Mol Ther"},{"key":"10.1016\/j.cjtee.2025.08.001_bib8","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cjtee.2022.06.002","article-title":"Recent advances in neutrophil chemotaxis abnormalities during sepsis","volume":"25","author":"Zhou","year":"2022","journal-title":"Chin J Traumatol (Engl Ed)"},{"key":"10.1016\/j.cjtee.2025.08.001_bib9","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1097\/TA.0b013e318256e000","article-title":"Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care","volume":"72","author":"Gentile","year":"2012","journal-title":"J Trauma Acute Care Surg"},{"key":"10.1016\/j.cjtee.2025.08.001_bib10","article-title":"Immune checkpoints: novel therapeutic targets to attenuate sepsis-induced immunosuppression","volume":"11","author":"McBride","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib11","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.immuni.2024.01.010","article-title":"LAG-3, TIM-3, and TIGIT: distinct functions in immune regulation","volume":"57","author":"Joller","year":"2024","journal-title":"Immunity"},{"key":"10.1016\/j.cjtee.2025.08.001_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2021.107933","article-title":"TIM-3: an update on immunotherapy","volume":"99","author":"Zhao","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib13","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/415536a","article-title":"Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease","volume":"415","author":"Monney","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.cjtee.2025.08.001_bib14","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.adf2223","article-title":"Beyond T cell exhaustion: TIM-3 regulation of myeloid cells","volume":"9","author":"Dixon","year":"2024","journal-title":"Sci Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib15","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1182\/bloodadvances.2022008854","article-title":"Association of TIM-3 checkpoint receptor expression on T cells with treatment-free remission in chronic myeloid leukemia","volume":"7","author":"Irani","year":"2023","journal-title":"Blood Adv"},{"key":"10.1016\/j.cjtee.2025.08.001_bib16","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s12967-024-05002-3","article-title":"Diffuse large B-cell lymphoma: the significance of CD8(+) tumor-infiltrating lymphocytes exhaustion mediated by TIM3\/Galectin-9 pathway","volume":"22","author":"Zhu","year":"2024","journal-title":"J Transl Med"},{"key":"10.1016\/j.cjtee.2025.08.001_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.110418","article-title":"T-cell immunoglobulin and mucin-domain containing-3 (TIM-3): solving a key puzzle in autoimmune diseases","volume":"121","author":"Chen","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib18","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.humimm.2014.02.001","article-title":"Tim-3 signaling pathway as a novel negative mediator in lipopolysaccharide-induced endotoxic shock","volume":"75","author":"Wang","year":"2014","journal-title":"Hum Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2019.105803","article-title":"Assessment of serum Tim-3 and Gal-9 levels in predicting the risk of infection after kidney transplantation","volume":"75","author":"Li","year":"2019","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib20","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fcimb.2017.00098","article-title":"Modulation of Tim-3 expression by antigen-dependent and -Independent factors on T cells from patients with chronic hepatitis B virus infection","volume":"7","author":"Dong","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib21","doi-asserted-by":"crossref","DOI":"10.1177\/20587384211061051","article-title":"Splenic CD4(+) and CD8(+) T-cells highly expressed PD-1 and Tim-3 in cirrhotic patients with HCV infection and portal hypertension","volume":"35","author":"Huang","year":"2021","journal-title":"Int J Immunopathol Pharmacol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib22","doi-asserted-by":"crossref","first-page":"9122","DOI":"10.1128\/JVI.00639-09","article-title":"Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells","volume":"83","author":"Golden-Mason","year":"2009","journal-title":"J Virol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0040146","article-title":"Tim-3 negatively regulates cytotoxicity in exhausted CD8+ T cells in HIV infection","volume":"7","author":"Sakhdari","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.cjtee.2025.08.001_bib24","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/infdis\/jiw428","article-title":"T-Cell Immunoglobulin- and mucin-domain-containing molecule 3 signaling blockade improves cell-mediated immunity against malaria","volume":"214","author":"Hou","year":"2016","journal-title":"J Infect Dis"},{"key":"10.1016\/j.cjtee.2025.08.001_bib25","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.3389\/fmicb.2017.01431","article-title":"Down-Regulation of Tim-3 in monocytes and macrophages in plasmodium infection and its Association with parasite clearance","volume":"8","author":"Hou","year":"2017","journal-title":"Front Microbiol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib26","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41420-023-01519-6","article-title":"Tim-3 protects against cisplatin nephrotoxicity by inhibiting NF-\u03baB-mediated inflammation","volume":"9","author":"Li","year":"2023","journal-title":"Cell Death Discov"},{"key":"10.1016\/j.cjtee.2025.08.001_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.clim.2022.109185","article-title":"Tim-3: an inhibitory immune checkpoint is associated with maternal-fetal tolerance and recurrent spontaneous abortion","volume":"245","author":"Zhu","year":"2022","journal-title":"Clin Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib28","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.3389\/fimmu.2019.01550","article-title":"Role of Tim-3 in decidual macrophage functional polarization during abnormal pregnancy with Toxoplasma gondii infection","volume":"10","author":"Zhang","year":"2019","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib29","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1186\/s40001-024-02203-w","article-title":"Tim-3 pathway dysregulation and targeting in sepsis-induced immunosuppression","volume":"29","author":"Luo","year":"2024","journal-title":"Eur J Med Res"},{"key":"10.1016\/j.cjtee.2025.08.001_bib30","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1469794","article-title":"Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma","volume":"15","author":"Shil","year":"2024","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41577-019-0224-6","article-title":"TIM3 comes of age as an inhibitory receptor","volume":"20","author":"Wolf","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib32","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/ni1271","article-title":"The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity","volume":"6","author":"Zhu","year":"2005","journal-title":"Nat Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib33","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.1182\/blood-2011-11-389585","article-title":"Galectin-9 binding to Tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection","volume":"119","author":"Elahi","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.cjtee.2025.08.001_bib34","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cellimm.2011.03.005","article-title":"Tim-3 ligand galectin-9 reduces IL-17 level and accelerates Klebsiella pneumoniae infection","volume":"269","author":"Wang","year":"2011","journal-title":"Cell Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib35","doi-asserted-by":"crossref","DOI":"10.1186\/cc13147","article-title":"Galectin-9 prolongs the survival of septic mice by expanding Tim-3-expressing natural killer T cells and PDCA-1+ CD11c+ macrophages","volume":"17","author":"Kadowaki","year":"2013","journal-title":"Crit Care"},{"key":"10.1016\/j.cjtee.2025.08.001_bib36","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.clim.2018.04.010","article-title":"Alpha-lactose reverses liver injury via blockade of Tim-3-mediated CD8 apoptosis in sepsis","volume":"192","author":"Wei","year":"2018","journal-title":"Clin Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib37","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.tice.2015.12.007","article-title":"Role of PI3K\/Akt signal pathway on proliferation of mesangial cell induced by HMGB1","volume":"48","author":"Feng","year":"2016","journal-title":"Tissue Cell"},{"key":"10.1016\/j.cjtee.2025.08.001_bib38","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.canlet.2012.02.014","article-title":"HMGB-1 induces cell motility and \u03b15\u03b21 integrin expression in human chondrosarcoma cells","volume":"322","author":"Tang","year":"2012","journal-title":"Cancer Lett"},{"key":"10.1016\/j.cjtee.2025.08.001_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellimm.2020.104192","article-title":"HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs","volume":"356","author":"Li","year":"2020","journal-title":"Cell Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib40","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2147\/JIR.S302967","article-title":"HMGB1\/TLR4 signaling affects regulatory T cells in Acute lung injury","volume":"14","author":"Zhou","year":"2021","journal-title":"J Inflamm Res"},{"key":"10.1016\/j.cjtee.2025.08.001_bib41","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1021\/jacs.1c11498","article-title":"Photophosphatidylserine guides natural killer cell photoimmunotherapy via Tim-3","volume":"144","author":"Yang","year":"2022","journal-title":"J Am Chem Soc"},{"key":"10.1016\/j.cjtee.2025.08.001_bib42","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.biophys.093008.131234","article-title":"The distribution and function of phosphatidylserine in cellular membranes","volume":"39","author":"Leventis","year":"2010","journal-title":"Annu Rev Biophys"},{"key":"10.1016\/j.cjtee.2025.08.001_bib43","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.4049\/jimmunol.0903059","article-title":"T cell\/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells","volume":"184","author":"DeKruyff","year":"2010","journal-title":"J Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib44","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01999-19","article-title":"HIV-1 vpu downregulates Tim-3 from the surface of infected CD4(+) T cells","volume":"94","author":"Pr\u00e9vost","year":"2020","journal-title":"J Virol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib45","doi-asserted-by":"crossref","first-page":"5139","DOI":"10.4049\/jimmunol.168.10.5139","article-title":"Carcinoembryonic antigen-related cell adhesion molecule 1 expression and signaling in human, mouse, and rat leukocytes: evidence for replacement of the short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked proteins in human leukocytes","volume":"168","author":"Singer","year":"2002","journal-title":"J Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib46","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1172\/JCI24340","article-title":"Carcinoembryonic antigen-related cell adhesion molecule 1 modulates vascular remodeling in vitro and in vivo","volume":"116","author":"Horst","year":"2006","journal-title":"J Clin Investig"},{"key":"10.1016\/j.cjtee.2025.08.001_bib47","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/nature13848","article-title":"CEACAM1 regulates TIM-3-mediated tolerance and exhaustion","volume":"517","author":"Huang","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.cjtee.2025.08.001_bib48","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00705-023-05842-2","article-title":"Role of Tim-3 in COVID-19: a potential biomarker and therapeutic target","volume":"168","author":"Ma","year":"2023","journal-title":"Arch Virol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib49","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3389\/fimmu.2018.00686","article-title":"Adaptive NKG2C(+)CD57(+) natural killer cell and Tim-3 expression during viral infections","volume":"9","author":"Kared","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib50","doi-asserted-by":"crossref","DOI":"10.1080\/0886022X.2023.2187229","article-title":"Mesenchymal stem cells protect against sepsis-associated acute kidney injury by inducing Gal-9\/Tim-3 to remodel immune homeostasis","volume":"45","author":"Luo","year":"2023","journal-title":"Ren Fail"},{"key":"10.1016\/j.cjtee.2025.08.001_bib51","article-title":"Recurrent Sepsis exacerbates CD4(+) T cell exhaustion and decreases antiviral immune responses","volume":"12","author":"He","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib52","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.3390\/ijms18112413","article-title":"Targeting immune cell checkpoints during sepsis","volume":"18","author":"Patil","year":"2017","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.cjtee.2025.08.001_bib53","article-title":"Multifunctional nanoparticles confers both multiple inflammatory mediators scavenging and macrophage polarization for sepsis therapy","volume":"30","author":"Xi","year":"2025","journal-title":"Mater Today Bio"},{"key":"10.1016\/j.cjtee.2025.08.001_bib54","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41467-021-21066-x","article-title":"High-throughput phenotypic screen and transcriptional analysis identify new compounds and targets for macrophage reprogramming","volume":"12","author":"Hu","year":"2021","journal-title":"Nat Commun"},{"key":"10.1016\/j.cjtee.2025.08.001_bib55","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.4049\/jimmunol.1202661","article-title":"T cell Ig mucin-3 promotes homeostasis of sepsis by negatively regulating the TLR response","volume":"190","author":"Yang","year":"2013","journal-title":"J Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib56","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2023.115087","article-title":"Dynamics of the inhibitory immune checkpoint TIM-3 in mouse pulmonary phagocytes after silica exposure","volume":"261","author":"Zhao","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"key":"10.1016\/j.cjtee.2025.08.001_bib57","article-title":"Tim-3 inhibits macrophage control of Listeria monocytogenes by inhibiting Nrf2","volume":"7","author":"Wang","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.cjtee.2025.08.001_bib58","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellimm.2024.104889","article-title":"Ubiquitination and degradation of MHC-II by Tim-3 inhibits antiviral immunity","volume":"407","author":"Zhou","year":"2025","journal-title":"Cell Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib59","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1146\/annurev-immunol-101819-025146","article-title":"Dendritic cell regulation of T helper cells","volume":"39","author":"Yin","year":"2021","journal-title":"Annu Rev Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib60","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/imr.12520","article-title":"Tim-3 and its role in regulating anti-tumor immunity","volume":"276","author":"Das","year":"2017","journal-title":"Immunol Rev"},{"key":"10.1016\/j.cjtee.2025.08.001_bib61","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.4049\/jimmunol.1601298","article-title":"Tim-3 is a marker of plasmacytoid dendritic cell dysfunction during HIV infection and is associated with the recruitment of IRF7 and p85 into lysosomes and with the submembrane displacement of TLR9","volume":"198","author":"Schwartz","year":"2017","journal-title":"J Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib62","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41577-019-0139-2","article-title":"Immunometabolism and natural killer cell responses","volume":"19","author":"O'Brien","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib63","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s12943-024-02045-4","article-title":"Natural killer cell-derived exosome-based cancer therapy: from biological roles to clinical significance and implications","volume":"23","author":"Si","year":"2024","journal-title":"Mol Cancer"},{"key":"10.1016\/j.cjtee.2025.08.001_bib64","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41586-023-06945-1","article-title":"Natural killer cell therapies","volume":"626","author":"Vivier","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.cjtee.2025.08.001_bib65","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.cyto.2015.05.012","article-title":"Tim-3 pathway affects NK cell impairment in patients with active tuberculosis","volume":"76","author":"Wang","year":"2015","journal-title":"Cytokine"},{"key":"10.1016\/j.cjtee.2025.08.001_bib66","article-title":"The role of TIM-3 in sepsis: a promising target for immunotherapy","volume":"15","author":"Wang","year":"2024","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib67","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0110585","article-title":"Tim-3 negatively mediates natural killer cell function in LPS-induced endotoxic shock","volume":"9","author":"Hou","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.cjtee.2025.08.001_bib68","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.1182\/blood-2011-11-392951","article-title":"Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity","volume":"119","author":"Ndhlovu","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.cjtee.2025.08.001_bib69","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1097\/QAD.0000000000002165","article-title":"Soluble plasma programmed death 1 (PD-1) and Tim-3 in primary HIV infection","volume":"33","author":"Zilber","year":"2019","journal-title":"AIDS"},{"key":"10.1016\/j.cjtee.2025.08.001_bib70","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.637809","article-title":"Regulation of Th1 T cell differentiation by iron via upregulation of T cell immunoglobulin and mucin containing Protein-3 (TIM-3)","volume":"12","author":"Pfeifhofer-Obermair","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib71","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12072-018-9867-9","article-title":"Immune checkpoint receptors: homeostatic regulators of immunity","volume":"12","author":"Riva","year":"2018","journal-title":"Hepatol Int"},{"key":"10.1016\/j.cjtee.2025.08.001_bib72","first-page":"827","article-title":"High expression of Tim-3 in alveolar echinococcosis mediates depletion of CD8(+) T cell function","volume":"51","author":"Zhao","year":"2021","journal-title":"Ann Clin Lab Sci"},{"key":"10.1016\/j.cjtee.2025.08.001_bib73","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.adp7302","article-title":"Palmitoylation of TIM-3 promotes immune exhaustion and restrains antitumor immunity","volume":"9","author":"Zhang","year":"2024","journal-title":"Sci Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib74","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.4251\/wjgo.v15.i12.2138","article-title":"Combined TIM-3 and PD-1 blockade restrains hepatocellular carcinoma development by facilitating CD4+ and CD8+ T cell-mediated antitumor immune responses","volume":"15","author":"Zhang","year":"2023","journal-title":"World J Gastrointest Oncol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib75","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s43556-025-00267-6","article-title":"TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives","volume":"6","author":"Yan","year":"2025","journal-title":"Mol Biomed"},{"key":"10.1016\/j.cjtee.2025.08.001_bib76","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.canlet.2021.04.011","article-title":"The TIM3\/Gal9 signaling pathway: an emerging target for cancer immunotherapy","volume":"510","author":"Kandel","year":"2021","journal-title":"Cancer Lett"},{"key":"10.1016\/j.cjtee.2025.08.001_bib77","doi-asserted-by":"crossref","first-page":"14733","DOI":"10.1073\/pnas.1009731107","article-title":"Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection","volume":"107","author":"Jin","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.cjtee.2025.08.001_bib78","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13613-022-00982-1","article-title":"Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients","volume":"12","author":"Bidar","year":"2022","journal-title":"Ann Intensive Care"},{"key":"10.1016\/j.cjtee.2025.08.001_bib79","doi-asserted-by":"crossref","DOI":"10.1186\/cc11404","article-title":"A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis","volume":"16","author":"Boomer","year":"2012","journal-title":"Crit Care"},{"key":"10.1016\/j.cjtee.2025.08.001_bib80","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/1632902","article-title":"Immune checkpoint receptors Tim-3 and PD-1 regulate Monocyte and T lymphocyte function in septic patients","volume":"2018","author":"Xia","year":"2018","journal-title":"Mediat Inflamm"},{"key":"10.1016\/j.cjtee.2025.08.001_bib81","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aba0717","article-title":"The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse","volume":"14","author":"Kataoka","year":"2021","journal-title":"Sci Signal"},{"key":"10.1016\/j.cjtee.2025.08.001_bib82","doi-asserted-by":"crossref","DOI":"10.1016\/j.clim.2023.109249","article-title":"Immune checkpoint molecule Tim-3 promotes NKT cell apoptosis and predicts poorer prognosis in Sepsis","volume":"254","author":"Wu","year":"2023","journal-title":"Clin Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib83","article-title":"Increased expression of Tim-3 is associated with depletion of NKT cells in SARS-CoV-2 infection","volume":"13","author":"Yang","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib84","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00436-015-4784-5","article-title":"Increased Gal-9 and Tim-3 expressions during liver damage in a murine malarial model","volume":"115","author":"Xiao","year":"2016","journal-title":"Parasitol Res"},{"key":"10.1016\/j.cjtee.2025.08.001_bib85","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/imm.12890","article-title":"Acute stimulation generates Tim-3-expressing T helper type 1 CD4 T cells that persist in vivo and show enhanced effector function","volume":"154","author":"Gorman","year":"2018","journal-title":"Immunology"},{"key":"10.1016\/j.cjtee.2025.08.001_bib86","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.4049\/jimmunol.1302290","article-title":"Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection","volume":"192","author":"Gorman","year":"2014","journal-title":"J Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib87","first-page":"830","article-title":"Tim-3 promotes Listeria monocytogenes immune evasion by suppressing major histocompatibility complex class I","volume":"221","author":"Wang","year":"2020","journal-title":"J Infect Dis"},{"key":"10.1016\/j.cjtee.2025.08.001_bib88","first-page":"1189","article-title":"Tim-3 promotes maternal tolerance","volume":"18","author":"Dempsey","year":"2017","journal-title":"Nat Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib89","doi-asserted-by":"crossref","first-page":"9378","DOI":"10.3390\/ijms25179378","article-title":"Surface immune checkpoints as potential biomarkers in physiological pregnancy and recurrent pregnancy loss","volume":"25","author":"Zych","year":"2024","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.cjtee.2025.08.001_bib90","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.940835","article-title":"Early detection of soluble CD27, BTLA, and TIM-3 predicts the development of nosocomial infection in pediatric burn patients","volume":"13","author":"Penatzer","year":"2022","journal-title":"Front Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib91","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/cei.12401","article-title":"Blockade of the T cell immunoglobulin and mucin domain protein 3 pathway exacerbates sepsis-induced immune deviation and immunosuppression","volume":"178","author":"Zhao","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib92","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12873-022-00733-2","article-title":"Role of CD8(+) T cell exhaustion in the progression and prognosis of acute respiratory distress syndrome induced by sepsis: a prospective observational study","volume":"22","author":"Yan","year":"2022","journal-title":"BMC Emerg Med"},{"key":"10.1016\/j.cjtee.2025.08.001_bib93","doi-asserted-by":"crossref","first-page":"89","DOI":"10.36401\/JIPO-23-4","article-title":"T cell Immunoglobulin and mucin domain containing protein 3 (TIM-3) inhibitors in oncology clinical trials: a review","volume":"7","author":"Duong","year":"2024","journal-title":"J Immunother Precis Oncol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib94","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1038\/s41375-025-02642-2","article-title":"KK2845, a PBD dimer-containing antibody-drug conjugate targeting TIM-3-expressing AML","volume":"39","author":"Zou","year":"2025","journal-title":"Leukemia"},{"key":"10.1016\/j.cjtee.2025.08.001_bib95","doi-asserted-by":"crossref","DOI":"10.1111\/sji.12738","article-title":"Monoclonal antibody against human Tim-3 enhances antiviral immune response","volume":"89","author":"Li","year":"2019","journal-title":"Scand J Immunol"},{"key":"10.1016\/j.cjtee.2025.08.001_bib96","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1097\/SHK.0000000000000717","article-title":"\u03b1-Lactose improves the survival of septic mice by blockade of TIM-3 signaling to prevent NKT cell apoptosis and attenuate cytokine storm","volume":"47","author":"Yao","year":"2017","journal-title":"Shock"},{"key":"10.1016\/j.cjtee.2025.08.001_bib97","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cjtee.2023.11.001","article-title":"Clinical practice of sepsis-induced immunosuppression: current immunotherapy and future options","volume":"27","author":"Pei","year":"2024","journal-title":"Chin J Traumatol (Engl Ed)"}],"container-title":["Chinese Journal of Traumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1008127525001099?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1008127525001099?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T19:36:55Z","timestamp":1782329815000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1008127525001099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":97,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["S1008127525001099"],"URL":"https:\/\/doi.org\/10.1016\/j.cjtee.2025.08.001","relation":{},"ISSN":["1008-1275"],"issn-type":[{"value":"1008-1275","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TIM-3, a potential target for sepsis therapy","name":"articletitle","label":"Article Title"},{"value":"Chinese Journal of Traumatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cjtee.2025.08.001","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Chinese Medical Association. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}