{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:40:06Z","timestamp":1792068006898,"version":"4.4.0"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100006049","name":"Comisi\u00f3n Sectorial de Investigaci\u00f3n Cient\u00edfica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Dendritic cells (DCs) orchestrate antitumor immunity by integrating signals from the tumor microenvironment to prime effective T cell responses. Many tumors display altered glycosylation patterns, including tumor-associated carbohydrate antigens (TACAs) such as the Tn antigen (GalNAc\u03b11-\n                    <jats:italic toggle=\"yes\">O<\/jats:italic>\n                    -Ser\/Thr); yet how these structures influence DC function is not well defined. Here, we investigated how Tn-bearing glycoconjugates modulate DC activation and shape adaptive immunity. Bone marrow-derived DCs (BMDCs) efficiently internalized fluorescently labeled Tn-glycoconjugates, whereas uptake of non-glycosylated counterparts was negligible. Although Tn-glycoconjugates alone did not induce DC maturation, co-stimulation with the Toll-like receptor 9 (TLR9) agonist CpG markedly increased CD86 expression and the secretion of IL-12\/23p40 and IL-6, with the multivalent construct MAG:Tn3-PV eliciting the strongest response. These conditioned BMDCs promoted strong IFN-\u03b3 production by allogeneic splenocytes, consistent with a Th1-polarizing phenotype. Mechanistically, both uptake and CpG-enhanced activation required the C-type lectin receptor MGL2, as blockade of MGL or competition with GalNAc abrogated glycoconjugate uptake and CpG-enhanced cytokine induction. Pharmacological inhibition revealed that MGL2 signaling synergizes with TLR9 through the Syk\u2013Raf-1\u2013NF-\u03baB axis.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    , mice immunized with DCs conditioned with Tn-glycoconjugate- plus CpG displayed enhanced splenocyte proliferation, increased IFN-\u03b3 secretion, and elevated cytotoxic activity without IL-10 induction, confirming a Th1-skewed response. Collectively, these findings identify MGL2 as a critical mediator of Tn-glycoconjugate sensing and unveil a synergistic C-type lectin receptor (CLR)\u2013TLR9 cross-talk that amplifies DC maturation and cytotoxic immunity. This study provides mechanistic insight into how specific glycan\u2013lectin interactions fine-tune innate receptor signaling, highlighting the potential of Tn-based glycoconjugates as immunomodulatory tools for vaccine design and cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1177\/17534259261449674","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T11:26:57Z","timestamp":1778498817000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Tn-Glycoconjugates engage MGL2 to potentiate TLR9-mediated dendritic cell maturation and Th1-skewed immune responses"],"prefix":"10.1177","volume":"32","author":[{"given":"Carolina","family":"Chiale","sequence":"first","affiliation":[{"name":"Universidad de la Rep\u00fablica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Bay","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3523"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Ganneau","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UMR3523"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-8845","authenticated-orcid":false,"given":"Teresa","family":"Freire","sequence":"additional","affiliation":[{"name":"Universidad de la Rep\u00fablica"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16050981"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03059"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16122211"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1001294"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.5MR0217-059RR"},{"issue":"3","key":"e_1_3_2_7_2","first-page":"590","article-title":"Dendritic cells in anticancer vaccination: Rationale for ex vivo loading or in vivo targeting","volume":"9","author":"Baldin A","year":"2020","unstructured":"Baldin A, Savvateeva LV, Bazhin AV, et al. Dendritic cells in anticancer vaccination: Rationale for ex vivo loading or in vivo targeting. 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IFN-\u03b3: central regulator of antitumor immunity. Front Immunol 2018; 9: 2132.","journal-title":"Front Immunol"},{"key":"e_1_3_2_37_2","first-page":"109961","article-title":"Heterogeneity and plasticity of Th1 cells in the tumor microenvironment","volume":"82","author":"Zhu J","year":"2021","unstructured":"Zhu J, Paul WE. Heterogeneity and plasticity of Th1 cells in the tumor microenvironment. Cell Signal 2021; 82: 109961.","journal-title":"Cell Signal"},{"key":"e_1_3_2_38_2","first-page":"45","article-title":"IFN-\u03b3-mediated apoptosis in tumor cells and its implications for immune therapy","volume":"12","author":"Kim SH","year":"2023","unstructured":"Kim SH, Lee JH. IFN-\u03b3-mediated apoptosis in tumor cells and its implications for immune therapy. PMC Immunology 2023; 12: 45\u201356.","journal-title":"PMC Immunology"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.209742"}],"container-title":["Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17534259261449674","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/17534259261449674","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/17534259261449674","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T11:26:59Z","timestamp":1778930819000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/17534259261449674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":38,"alternative-id":["10.1177\/17534259261449674"],"URL":"https:\/\/doi.org\/10.1177\/17534259261449674","relation":{},"ISSN":["1753-4259","1753-4267"],"issn-type":[{"value":"1753-4259","type":"print"},{"value":"1753-4267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"article-number":"17534259261449674"}}