{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:01:38Z","timestamp":1790359298076,"version":"4.1.0"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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":["32100742"],"award-info":[{"award-number":["32100742"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Research Program of Shanxi Province","award":["202403021211194"],"award-info":[{"award-number":["202403021211194"]}]},{"DOI":"10.13039\/501100013317","name":"Shanxi Provincial Key Research and Development Project","doi-asserted-by":"publisher","award":["202302130501010"],"award-info":[{"award-number":["202302130501010"]}],"id":[{"id":"10.13039\/501100013317","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Pro-inflammatory M1 polarization of adipose tissue macrophages (ATMs) drives adipose inflammation and obesity, suggesting that reprogramming ATM polarization holds therapeutic promise. Parasitic helminths have co-evolved with hosts to induce immune tolerance via M2 polarization, making helminth-derived M2-inducing molecules a potential therapeutic strategy against metabolic disorders. This study aimed to develop a defined serine protease inhibitor derived from\n                    <jats:italic>Trichinella spiralis<\/jats:italic>\n                    (Ts-SPI) as a novel immunomodulatory candidate against diet-induced metabolic disorders. In a high-fat diet (HFD)-induced obese mouse model, recombinant Ts-SPI (rTs-SPI) attenuated obesity and adipose tissue inflammation, and this effect was associated with its ability to reprogram macrophage polarization.\n                    <jats:italic>In vitro<\/jats:italic>\n                    studies confirmed that rTs-SPI drives phenotypic changes in both RAW264.7 cells and bone marrow-derived macrophages (BMDMs). Notably, a free fatty acid (FFA)-stimulated inflammatory adipocyte model and adoptive transfer assays demonstrated that rTs-SPI-reprogrammed macrophages mediate the anti-obesity and anti-inflammatory effects. Mechanistically, TIM-3 was identified as a key mediator through\n                    <jats:italic>in vivo<\/jats:italic>\n                    TIM-3 blockade assays. Pharmacological inhibition revealed downstream PI3K\/AKT\/mTOR signaling. In summary, this study identifies a parasite-derived protein as a potent TIM-3-targeting biologic candidate for treating metabolic inflammation, proposes a novel \u201chelminth-inspired checkpoint modulation\u201d strategy, and provides new insight into parasite-host immune crosstalk.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014606","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:41:33Z","timestamp":1790358093000},"page":"e1014606","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serine protease inhibitor from Trichinella spiralis ameliorates diet-induced obesity and adipose tissue inflammation through TIM-3-dependent macrophage reprogramming"],"prefix":"10.1371","volume":"22","author":[{"given":"Mingwei","family":"Tong","sequence":"first","affiliation":[{"name":"First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"],"department":["Department of Endocrinology"]},{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["School of Basic Medical Sciences"]},{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["Shanxi Key Laboratory of Metabolic-Immune Homeostasis and Drug Innovation"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["School of Basic Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guidong","family":"Ren","sequence":"additional","affiliation":[{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["School of Basic Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangxuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["School of Basic Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyu","family":"Qiao","sequence":"additional","affiliation":[{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["School of Basic Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["School of Basic Medical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Fan","sequence":"additional","affiliation":[{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["School of Basic Medical Sciences"]},{"name":"Shanxi Medical University","place":["Jinzhong, China"],"department":["Shanxi Key Laboratory of Metabolic-Immune Homeostasis and Drug Innovation"]},{"name":"Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, and Shanxi Key Laboratory of Cellular Physiology","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"],"department":["Department of Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-2039","authenticated-orcid":true,"given":"Yong","family":"Yang","sequence":"additional","affiliation":[{"name":"First Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"],"department":["Department of Infectious Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"3","key":"ppat.1014606.ref001","article-title":"Integrated omics analysis reveals the alteration of gut microbe-metabolites in obese adults","volume":"22","author":"R Li","year":"2021","journal-title":"Brief Bioinform"},{"issue":"11","key":"ppat.1014606.ref002","first-page":"656","article-title":"Obesity - a chronic disease requiring treatment","volume":"147","author":"S Meyh\u00f6fer","year":"2022","journal-title":"Dtsch Med Wochenschr"},{"key":"ppat.1014606.ref003","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.semcancer.2025.03.007","article-title":"Vitamin D: What role in obesity-related cancer?","volume":"112","author":"P Martinez","year":"2025","journal-title":"Semin Cancer Biol"},{"key":"ppat.1014606.ref004","doi-asserted-by":"crossref","first-page":"111315","DOI":"10.1016\/j.biopha.2021.111315","article-title":"Adipose tissue and insulin resistance in obese","volume":"137","author":"B Ahmed","year":"2021","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"ppat.1014606.ref005","article-title":"Inflammation-mediated metabolic regulation in adipose tissue","volume":"25","author":"S Xu","year":"2024","journal-title":"Obes Rev"},{"issue":"1","key":"ppat.1014606.ref006","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/imr.12853","article-title":"Adipose tissue macrophages: Unique polarization and bioenergetics in obesity","volume":"295","author":"HL Caslin","year":"2020","journal-title":"Immunol Rev"},{"issue":"9","key":"ppat.1014606.ref007","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.3390\/cells11091424","article-title":"New Insights into Adipose Tissue Macrophages in Obesity and Insulin Resistance","volume":"11","author":"Z Cai","year":"2022","journal-title":"Cells"},{"issue":"12","key":"ppat.1014606.ref008","doi-asserted-by":"crossref","first-page":"5428","DOI":"10.7150\/ijbs.115672","article-title":"WTAP Maintains Alternative Activation of Macrophages by Promoting IDH1-Mediated \u03b1-ketoglutarate Production","volume":"21","author":"Q Xu","year":"2025","journal-title":"Int J Biol Sci"},{"key":"ppat.1014606.ref009","doi-asserted-by":"crossref","first-page":"827486","DOI":"10.3389\/fimmu.2022.827486","article-title":"Helminth and host crosstalk: new insight into treatment of obesity and its associated metabolic syndromes","volume":"13","author":"M Dai","year":"2022","journal-title":"Front Immunol"},{"issue":"1","key":"ppat.1014606.ref010","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev-nutr-061121-100742","article-title":"Helminth infections and diabetes: mechanisms accounting for risk amelioration","volume":"44","author":"A Rajamanickam","year":"2024","journal-title":"Annu Rev Nutr"},{"key":"ppat.1014606.ref011","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.phrs.2018.04.008","article-title":"Helminth infection in mice improves insulin sensitivity via modulation of gut microbiota and fatty acid metabolism","volume":"132","author":"F Pace","year":"2018","journal-title":"Pharmacol Res"},{"issue":"4","key":"ppat.1014606.ref012","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41423-023-00979-1","article-title":"Maternal helminth infection protects offspring from high-fat-diet-induced obesity through altered microbiota and SCFAs","volume":"20","author":"C-W Su","year":"2023","journal-title":"Cell Mol Immunol"},{"issue":"2","key":"ppat.1014606.ref013","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1021\/acsptsci.3c00276","article-title":"Effect of Trichinella spiralis-Derived Antigens on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice","volume":"7","author":"Y Yang","year":"2024","journal-title":"ACS Pharmacol Transl Sci"},{"issue":"5","key":"ppat.1014606.ref014","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nri1601","article-title":"A worm\u2019s eye view of the immune system: consequences for evolution of human autoimmune disease","volume":"5","author":"DW Dunne","year":"2005","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"ppat.1014606.ref015","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s11033-025-11301-9","article-title":"M2 macrophage polarization in allogeneic skin transplantation: from intrinsic mechanisms to clinical prospects for immune tolerance","volume":"53","author":"T Ma","year":"2025","journal-title":"Mol Biol Rep"},{"issue":"6","key":"ppat.1014606.ref016","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri2992","article-title":"Diversity and dialogue in immunity to helminths","volume":"11","author":"JE Allen","year":"2011","journal-title":"Nat Rev Immunol"},{"issue":"7","key":"ppat.1014606.ref017","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1096\/fj.14-266239","article-title":"Chronic helminth infection and helminth-derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice","volume":"29","author":"L Hussaarts","year":"2015","journal-title":"FASEB J"},{"key":"ppat.1014606.ref018","doi-asserted-by":"crossref","first-page":"109924","DOI":"10.1016\/j.intimp.2023.109924","article-title":"The Trichinella spiralis-derived antigens alleviate HFD-induced obesity and inflammation in mice","volume":"117","author":"M Tong","year":"2023","journal-title":"Int Immunopharmacol"},{"issue":"5","key":"ppat.1014606.ref019","article-title":"Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities","volume":"16","author":"SM Ryan","year":"2020","journal-title":"PLoS Pathog"},{"key":"ppat.1014606.ref020","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.micinf.2018.01.003","article-title":"Serine protease inhibitors containing a Kunitz domain: their role in modulation of host inflammatory responses and parasite survival","volume":"20","author":"MTQ de Magalh\u00e3es","year":"2018","journal-title":"Microbes Infect"},{"issue":"8","key":"ppat.1014606.ref021","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0008510","article-title":"Fasciola hepatica serine protease inhibitor family (serpins): Purposely crafted for regulating host proteases","volume":"14","author":"C De Marco Verissimo","year":"2020","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1014606.ref022","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.3389\/fmicb.2017.01834","article-title":"Recombinant Trichinella pseudospiralis serine protease inhibitors alter macrophage polarization in vitro","volume":"8","author":"N Xu","year":"2017","journal-title":"Front Microbiol"},{"issue":"5","key":"ppat.1014606.ref023","doi-asserted-by":"crossref","first-page":"963","DOI":"10.4049\/jimmunol.2000290","article-title":"The Anti-Inflammatory Immune Response in Early Trichinella spiralis Intestinal Infection Depends on Serine Protease Inhibitor-Mediated Alternative Activation of Macrophages","volume":"206","author":"N Xu","year":"2021","journal-title":"J Immunol"},{"issue":"1","key":"ppat.1014606.ref024","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1038\/s41598-020-60155-7","article-title":"Effect of T. spiralis Serine protease inhibitors on TNBS-induced experimental colitis mediated by Macrophages","volume":"10","author":"J Xu","year":"2020","journal-title":"Sci Rep"},{"key":"ppat.1014606.ref025","doi-asserted-by":"crossref","first-page":"116223","DOI":"10.1016\/j.biopha.2024.116223","article-title":"Serine protease inhibitor from the muscle larval Trichinella spiralis ameliorates non-alcoholic fatty liver disease in mice via anti-inflammatory properties and gut-liver crosstalk","volume":"172","author":"M Tong","year":"2024","journal-title":"Biomed Pharmacother"},{"issue":"2","key":"ppat.1014606.ref026","doi-asserted-by":"crossref","DOI":"10.3390\/ijms27020840","article-title":"TIM-3 macrophages: Insights into their role in cancer and inflammation","volume":"27","author":"A Maksimova","year":"2026","journal-title":"Int J Mol Sci"},{"issue":"1","key":"ppat.1014606.ref027","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3724\/abbs.2025235","article-title":"Immune checkpoint TIM-3 in tumor immunotherapy","volume":"58","author":"S Ma","year":"2026","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"issue":"3","key":"ppat.1014606.ref028","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.ymthe.2021.11.015","article-title":"Spatial distribution and functional analysis define the action pathway of Tim-3\/Tim-3 ligands in tumor development","volume":"30","author":"T Wang","year":"2022","journal-title":"Mol Ther"},{"issue":"11","key":"ppat.1014606.ref029","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/s41423-018-0032-0","article-title":"Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice","volume":"16","author":"X Du","year":"2019","journal-title":"Cell Mol Immunol"},{"issue":"6","key":"ppat.1014606.ref030","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1038\/s41366-018-0114-1","article-title":"MicroRNA-30 modulates metabolic inflammation by regulating Notch signaling in adipose tissue macrophages","volume":"42","author":"K Miranda","year":"2018","journal-title":"Int J Obes (Lond)"},{"issue":"1","key":"ppat.1014606.ref031","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41574-024-01047-y","article-title":"Inflammation and resolution in obesity","volume":"21","author":"M Sot\u00e1k","year":"2025","journal-title":"Nat Rev Endocrinol"},{"issue":"8","key":"ppat.1014606.ref032","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1038\/s41366-026-02130-2","article-title":"Obesity-induced intervertebral disk degeneration: pathophysiology and clinical implications","volume":"50","author":"PS Bharti","year":"2026","journal-title":"Int J Obes (Lond)"},{"issue":"5","key":"ppat.1014606.ref033","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41590-023-01479-0","article-title":"Macrophage function in adipose tissue homeostasis and metabolic inflammation","volume":"24","author":"T Chavakis","year":"2023","journal-title":"Nat Immunol"},{"issue":"1","key":"ppat.1014606.ref034","doi-asserted-by":"crossref","first-page":"2411453","DOI":"10.1080\/21623945.2024.2411453","article-title":"10-Gingerol reduces cytoplasmic lipid droplets and induces lipolysis in 3T3-L1 adipocytes","volume":"13","author":"ME Preciado-Ortiz","year":"2024","journal-title":"Adipocyte"},{"key":"ppat.1014606.ref035","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.molimm.2018.02.006","article-title":"miR-330-5p\/Tim-3 axis regulates macrophage M2 polarization and insulin resistance in diabetes mice","volume":"95","author":"J Sun","year":"2018","journal-title":"Mol Immunol"},{"issue":"2","key":"ppat.1014606.ref036","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":"Z Zhao","year":"2014","journal-title":"Clin Exp Immunol"},{"key":"ppat.1014606.ref037","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1146\/annurev-immunol-093019-122827","article-title":"Immune System Investigation Using Parasitic Helminths","volume":"39","author":"B Douglas","year":"2021","journal-title":"Annu Rev Immunol"},{"key":"ppat.1014606.ref038","doi-asserted-by":"crossref","first-page":"104751","DOI":"10.1016\/j.ebiom.2023.104751","article-title":"A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases","volume":"95","author":"Y Ni","year":"2023","journal-title":"EBioMedicine"},{"issue":"1","key":"ppat.1014606.ref039","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.1038\/s41467-025-60463-4","article-title":"TIM3-blockade synergizes with IL2 in alleviating intra-tumoral CD8+T cell exhaustion","volume":"16","author":"X Zhang","year":"2025","journal-title":"Nat Commun"},{"issue":"7534","key":"ppat.1014606.ref040","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/nature13848","article-title":"CEACAM1 regulates TIM-3-mediated tolerance and exhaustion","volume":"517","author":"Y-H Huang","year":"2015","journal-title":"Nature"},{"key":"ppat.1014606.ref041","doi-asserted-by":"crossref","first-page":"157095","DOI":"10.1016\/j.phymed.2025.157095","article-title":"Sophora Flos extract ameliorates inflammatory bowel disease via inhibiting the PI3K\/AKT\/mTOR signaling pathway activation and modulating M1\/M2 polarization in macrophages","volume":"146","author":"A Li","year":"2025","journal-title":"Phytomedicine"},{"issue":"30","key":"ppat.1014606.ref042","article-title":"Retinal microenvironment-protected rhein-gffye nanofibers attenuate retinal ischemia-reperfusion injury via inhibiting oxidative stress and regulating microglial\/macrophage m1\/m2 polarization","volume":"10","author":"Z Zhang","year":"2023","journal-title":"Advanced Science (Weinh)"},{"issue":"3","key":"ppat.1014606.ref043","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.bbamcr.2005.07.006","article-title":"Suppression of macrophage responses to bacterial lipopolysaccharide (LPS) by secretory leukocyte protease inhibitor (SLPI) is independent of its anti-protease function","volume":"1745","author":"J Yang","year":"2005","journal-title":"Biochim Biophys Acta"},{"issue":"5","key":"ppat.1014606.ref044","first-page":"886","article-title":"C1 inhibitor, a multi-functional serine protease inhibitor","volume":"104","author":"3rd Davis AE","year":"2010","journal-title":"Thromb Haemost"},{"key":"ppat.1014606.ref045","doi-asserted-by":"crossref","first-page":"109924","DOI":"10.1016\/j.intimp.2023.109924","article-title":"The Trichinella spiralis-derived antigens alleviate HFD-induced obesity and inflammation in mice","volume":"117","author":"M Tong","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"ppat.1014606.ref046","doi-asserted-by":"crossref","first-page":"116223","DOI":"10.1016\/j.biopha.2024.116223","article-title":"Serine protease inhibitor from the muscle larval Trichinella spiralis ameliorates non-alcoholic fatty liver disease in mice via anti-inflammatory properties and gut-liver crosstalk","volume":"172","author":"M Tong","year":"2024","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"ppat.1014606.ref047","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ijpara.2020.07.012","article-title":"Trichinella spiralis infection ameliorated diet-induced obesity model in mice","volume":"51","author":"SA Kang","year":"2021","journal-title":"Int J Parasitol"},{"issue":"17","key":"ppat.1014606.ref048","doi-asserted-by":"crossref","first-page":"6410","DOI":"10.3390\/molecules28176410","article-title":"Bilobalide Induces Apoptosis in 3T3-L1 Mature Adipocytes through ROS-Mediated Mitochondria Pathway","volume":"28","author":"S Bu","year":"2023","journal-title":"Molecules"},{"issue":"1","key":"ppat.1014606.ref049","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/s41467-018-03998-z","article-title":"Reduced oxidative capacity in macrophages results in systemic insulin resistance","volume":"9","author":"S-B Jung","year":"2018","journal-title":"Nat Commun"},{"issue":"1","key":"ppat.1014606.ref050","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.resp.2010.10.006","article-title":"Effects of bone marrow-derived mononuclear cells on airway and lung parenchyma remodeling in a murine model of chronic allergic inflammation","volume":"175","author":"SC Abreu","year":"2011","journal-title":"Respir Physiol Neurobiol"},{"issue":"14","key":"ppat.1014606.ref051","doi-asserted-by":"crossref","first-page":"7154","DOI":"10.7150\/thno.108173","article-title":"Artesunate-mycophenolate Mofetil Dimer Micelles Alleviate Allogeneic Skin Graft Rejection by Inhibiting the TLR-4 Pathway in Macrophages","volume":"15","author":"W Zhao","year":"2025","journal-title":"Theranostics"},{"issue":"1","key":"ppat.1014606.ref052","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/cei.13126","article-title":"Tim-3 exacerbates kidney ischaemia\/reperfusion injury through the TLR-4\/NF-\u03baB signalling pathway and an NLR-C4 inflammasome activation","volume":"193","author":"Y Guo","year":"2018","journal-title":"Clin Exp Immunol"},{"issue":"4","key":"ppat.1014606.ref053","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1080\/15548627.2022.2116833","article-title":"FOXP3+ macrophage represses acute ischemic stroke-induced neural inflammation","volume":"19","author":"W Cai","year":"2023","journal-title":"Autophagy"},{"issue":"4","key":"ppat.1014606.ref054","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.jcmgh.2021.12.010","article-title":"Metabolic Regulation of Macrophages by SIRT1 Determines Activation During Cholestatic Liver Disease in Mice","volume":"13","author":"A Isaacs-Ten","year":"2022","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"ppat.1014606.ref055","doi-asserted-by":"crossref","first-page":"6657658","DOI":"10.1155\/2021\/6657658","article-title":"Serum Fetuin-B Levels Are Elevated in Women with Metabolic Syndrome and Associated with Increased Oxidative Stress","volume":"2021","author":"S Xue","year":"2021","journal-title":"Oxid Med Cell Longev"},{"issue":"6","key":"ppat.1014606.ref056","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"DE Kleiner","year":"2005","journal-title":"Hepatology"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014606","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:41:42Z","timestamp":1790358102000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014606"}},"subtitle":[],"editor":[{"given":"Henry","family":"McSorley","sequence":"first","affiliation":[{"name":"University of Dundee","place":["UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014606","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]}}}