{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T19:42:34Z","timestamp":1772134954815,"version":"3.50.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Mol Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens. Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity\/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the\n                    <jats:italic>N<\/jats:italic>\n                    -glycosylation profile of thymocytes to high-mannose structures, using specific glycoengineered mice (\n                    <jats:italic>Rag1<\/jats:italic>\n                    <jats:sup>Cre<\/jats:sup>\n                    <jats:italic>Mgat1<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    ), we showed remarkable defects in key developmental checkpoints, including \u00df-selection, regulatory T-cell generation and \u03b3\u03b4T-cell development, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstrated that a single\n                    <jats:italic>N<\/jats:italic>\n                    -glycan antenna (modeled in\n                    <jats:italic>Rag1<\/jats:italic>\n                    <jats:sup>Cre<\/jats:sup>\n                    <jats:italic>Mgat2<\/jats:italic>\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    mice) is the\n                    <jats:italic>sine-qua-non<\/jats:italic>\n                    condition to ensure normal development. In conclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.\n                  <\/jats:p>","DOI":"10.1038\/s41423-023-01052-7","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T08:02:42Z","timestamp":1687334562000},"page":"955-968","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity"],"prefix":"10.1038","volume":"20","author":[{"given":"Manuel M.","family":"Vicente","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3914-7101","authenticated-orcid":false,"given":"In\u00eas","family":"Alves","sequence":"additional","affiliation":[]},{"given":"\u00c2ngela","family":"Fernandes","sequence":"additional","affiliation":[]},{"given":"Ana M.","family":"Dias","sequence":"additional","affiliation":[]},{"given":"Beatriz","family":"Santos-Pereira","sequence":"additional","affiliation":[]},{"given":"Elena","family":"P\u00e9rez-Anton","sequence":"additional","affiliation":[]},{"given":"Sofia","family":"Santos","sequence":"additional","affiliation":[]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[]},{"given":"Alexandra","family":"Correia","sequence":"additional","affiliation":[]},{"given":"Anja","family":"M\u00fcnster-K\u00fchnel","sequence":"additional","affiliation":[]},{"given":"Afonso R. M.","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Sarina","family":"Ravens","sequence":"additional","affiliation":[]},{"given":"Gabriel A.","family":"Rabinovich","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Vilanova","sequence":"additional","affiliation":[]},{"given":"Ana E.","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Salom\u00e9 S.","family":"Pinho","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"1052_CR1","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1146\/annurev-cellbio-092910-154008","volume":"27","author":"U Koch","year":"2011","unstructured":"Koch U, Radtke F. Mechanisms of T Cell Development and Transformation. 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Annu Rev Immunol. 2003;21:139\u201376. https:\/\/doi.org\/10.1146\/annurev.immunol.21.120601.141107","journal-title":"Annu Rev Immunol"},{"key":"1052_CR4","doi-asserted-by":"publisher","first-page":"7842","DOI":"10.3389\/fimmu.2018.02754","volume":"9","author":"MS Pereira","year":"2018","unstructured":"Pereira MS, Alves I, Vicente M, Campar A, Silva MC, Padrao NA, et al. Glycans as Key Checkpoints of T Cell Activity and Function. Front Immunol. 2018;9:7842\u201313. https:\/\/doi.org\/10.3389\/fimmu.2018.02754","journal-title":"Front Immunol"},{"key":"1052_CR5","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/nrc3982","volume":"15","author":"SS Pinho","year":"2015","unstructured":"Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. 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The study was approved by the Ethics Boards of the Faculty of Medicine of the University of Lisbon and of HSC.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}