{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:33Z","timestamp":1792788813461,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011396","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000}}],"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T00:00:00Z","timestamp":1683849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFC2300800, 2021YFC2300801, 2021YFC2300802"],"award-info":[{"award-number":["2021YFC2300800, 2021YFC2300801, 2021YFC2300802"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160396, 81760368"],"award-info":[{"award-number":["82160396, 81760368"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060370"],"award-info":[{"award-number":["82060370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cultivation projects of the National Science Fund for Distinguished Young Scholars","award":["xyd2021J003"],"award-info":[{"award-number":["xyd2021J003"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Infection with the cestode\n                    <jats:italic>Echinococcus multilocularis<\/jats:italic>\n                    (\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>multilocularis<\/jats:italic>\n                    ) causes alveolar echinococcosis (AE), a tumor-like disease predominantly affecting the liver but able to spread to any organ. T cells develop functional defects during chronic\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>multilocularis<\/jats:italic>\n                    infection, mostly due to upregulation of inhibitory receptors such as T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) and programmed death-1 (PD-1). However, the role of lymphocyte activation gene-3 (LAG3), an inhibitory receptor, in AE infection remains to be determined. Here, we discovered that high expression of LAG3 was mainly found in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and induced regulatory T cells (iTregs) in close liver tissue (CLT) from AE patients. In a mouse model of\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>multilocularis<\/jats:italic>\n                    infection, LAG3 expression was predominantly found in T helper 2 (Th2) and Treg subsets, which secreted significantly more IL-4 and IL-10, resulting in host immune tolerance and disease progression at a late stage. Furthermore, LAG3 deficiency was found to drive the development of effector memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and enhance the type 1 CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell immune response, thus inhibiting metacestode growth\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In addition, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from LAG3-deficient mice produced more IFN-\u03b3 and less IL-4 when stimulated by\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>multilocularis<\/jats:italic>\n                    protoscoleces (EmP) antigen\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Finally, adoptive transfer experiments showed that LAG3-knockout (KO) CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells were more likely to develop into Th1 cells and less likely to develop into Tregs in recipient mice. Our work reveals that high expression of LAG3 accelerates AE disease progression by modulating the immune imbalance of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell subsets. These findings may provide a novel immunotherapeutic strategy against\n                    <jats:italic>E<\/jats:italic>\n                    .\n                    <jats:italic>multilocularis<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011396","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T13:32:06Z","timestamp":1683898326000},"page":"e1011396","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Upregulation of LAG3 modulates the immune imbalance of CD4+ T-cell subsets and exacerbates disease progression in patients with alveolar echinococcosis and a mouse model"],"prefix":"10.1371","volume":"19","author":[{"given":"Dewei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abidan","family":"Ainiwaer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuran","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maolin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zibigu","family":"Rousu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinling","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejiao","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muesier","family":"Maimaiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3241-2224","authenticated-orcid":true,"given":"Chuanshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,12]]},"reference":[{"key":"ppat.1011396.ref001","doi-asserted-by":"crossref","first-page":"e3866","DOI":"10.1136\/bmj.e3866","article-title":"Diagnosis, 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