{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:37:28Z","timestamp":1768520248252,"version":"3.49.0"},"posted":{"date-parts":[[2025,1,3]]},"group-title":"Immunology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The role of immune cells in neurodegeneration remains incompletely understood. Our recent study revealed the presence of mucosal-associated invariant T (MAIT) cells in the meninges, where they express antioxidant molecules to maintain meningeal barrier integrity. Accumulation of misfolded tau proteins are a hallmark of neurodegenerative diseases. The role of MAIT cells in tau-related neuroinflammation and neurodegeneration, however, remains unclear. Here we report that the meninges of P301 mutant human tau transgenic mice had increased numbers of MAIT cells, which retained their expression of antioxidant molecules.\n                  <jats:italic>\n                    Mr1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  P301S mice that lacked MAIT cells exhibited increased tau pathology and hippocampus atrophy compared to control\n                  <jats:italic>Mr1<\/jats:italic>\n                  <jats:sup>+\/+<\/jats:sup>\n                  P301S mice. Adoptive transfer of MAIT cells reduced tau pathology and hippocampus atrophy in\n                  <jats:italic>\n                    Mr1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  P301S mice. Meningeal barrier integrity was compromised in\n                  <jats:italic>\n                    Mr\/\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  P301S mice, but not in control\n                  <jats:italic>Mr1<\/jats:italic>\n                  <jats:sup>+\/+<\/jats:sup>\n                  P301S mice. A distinctive microglia subset with proinflammatory gene expression profile (M-inflammatory) was enriched in the hippocampus of\n                  <jats:italic>\n                    Mr1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  P301S mice. The transcriptomes of the remaining microglia in these mice also shifted towards a proinflammatory state, with increased expression of inflammatory cytokines, chemokines, and genes related with ribosome biogenesis and immune responses to toxic substances. The transfer of MAIT cells restored meningeal barrier integrity and suppressed microglial inflammation in the\n                  <jats:italic>\n                    Mr1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  P301S mice. Together, our data indicate an important role for MAIT cells in regulating tau-pathology-related neuroinflammation and neurodegeneration.\n                <\/jats:p>","DOI":"10.1101\/2025.01.03.631124","type":"posted-content","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T14:45:12Z","timestamp":1735915512000},"source":"Crossref","is-referenced-by-count":0,"title":["MAIT cell deficiency exacerbates neuroinflammation in P301S human tau transgenic mice"],"prefix":"10.64898","author":[{"given":"Yuanyue","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaosheng","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaoyuan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025020923402245000_2025.01.03.631124v2.1","doi-asserted-by":"crossref","unstructured":"Samudra N , Lane-Donovan C , VandeVrede L , Boxer AL: Tau pathology in neurodegenerative disease: disease mechanisms and therapeutic avenues. J Clin Invest 2023, 133.","DOI":"10.1172\/JCI168553"},{"key":"2025020923402245000_2025.01.03.631124v2.2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410106"},{"key":"2025020923402245000_2025.01.03.631124v2.3","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.3.631"},{"key":"2025020923402245000_2025.01.03.631124v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.010"},{"key":"2025020923402245000_2025.01.03.631124v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-023-05788-0"},{"key":"2025020923402245000_2025.01.03.631124v2.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1333-19.2019"},{"key":"2025020923402245000_2025.01.03.631124v2.7","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv081"},{"key":"2025020923402245000_2025.01.03.631124v2.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4361-12.2013"},{"key":"2025020923402245000_2025.01.03.631124v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01415-3"},{"key":"2025020923402245000_2025.01.03.631124v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.05.070"},{"key":"2025020923402245000_2025.01.03.631124v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1895-7"},{"key":"2025020923402245000_2025.01.03.631124v2.12","doi-asserted-by":"publisher","DOI":"10.1159\/000486200"},{"key":"2025020923402245000_2025.01.03.631124v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.09.009"},{"key":"2025020923402245000_2025.01.03.631124v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-023-00882-y"},{"key":"2025020923402245000_2025.01.03.631124v2.15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01014"},{"key":"2025020923402245000_2025.01.03.631124v2.16","doi-asserted-by":"publisher","DOI":"10.1038\/nature11605"},{"key":"2025020923402245000_2025.01.03.631124v2.17","doi-asserted-by":"publisher","DOI":"10.1038\/nature01433"},{"key":"2025020923402245000_2025.01.03.631124v2.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01349-1"},{"key":"2025020923402245000_2025.01.03.631124v2.19","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02761-6"},{"key":"2025020923402245000_2025.01.03.631124v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.12.891"},{"key":"2025020923402245000_2025.01.03.631124v2.21","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0984"},{"key":"2025020923402245000_2025.01.03.631124v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/nature13160"},{"key":"2025020923402245000_2025.01.03.631124v2.23","doi-asserted-by":"crossref","unstructured":"Fung ITH , Sankar P , Zhang Y , Robison LS , Zhao X , D\u2019Souza SS , Salinero AE , Wang Y , Qian J , Kuentzel ML , et al: Activation of group 2 innate lymphoid cells alleviates aging-associated cognitive decline. J Exp Med 2020, 217.","DOI":"10.1084\/jem.20190915"},{"key":"2025020923402245000_2025.01.03.631124v2.24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000037"},{"key":"2025020923402245000_2025.01.03.631124v2.25","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02202-2"},{"key":"2025020923402245000_2025.01.03.631124v2.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.12.003"},{"key":"2025020923402245000_2025.01.03.631124v2.27","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13019"},{"key":"2025020923402245000_2025.01.03.631124v2.28","doi-asserted-by":"publisher","DOI":"10.1111\/all.14149"},{"key":"2025020923402245000_2025.01.03.631124v2.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708448114"},{"key":"2025020923402245000_2025.01.03.631124v2.30","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11484-E"},{"key":"2025020923402245000_2025.01.03.631124v2.31","first-page":"56440","article-title":"Ji S: Multiplex Cytokine Profiling of Stimulated Mouse Splenocytes Using a Cytometric Bead-based Immunoassay Platform","volume":"129","year":"2017","journal-title":"J Vis Exp"},{"key":"2025020923402245000_2025.01.03.631124v2.32","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz241"},{"key":"2025020923402245000_2025.01.03.631124v2.33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29552-6"},{"key":"2025020923402245000_2025.01.03.631124v2.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.022"},{"key":"2025020923402245000_2025.01.03.631124v2.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"},{"key":"2025020923402245000_2025.01.03.631124v2.36","doi-asserted-by":"crossref","unstructured":"Koay HF , Su S , Amann-Zalcenstein D , Daley SR , Comerford I , Miosge L , Whyte CE , Konstantinov IE , d\u2019Udekem Y , Baldwin T , et al: A divergent transcriptional landscape underpins the development and functional branching of MAIT cells. Sci Immunol 2019, 4.","DOI":"10.1126\/sciimmunol.aay6039"},{"key":"2025020923402245000_2025.01.03.631124v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0444-8"},{"key":"2025020923402245000_2025.01.03.631124v2.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01022-8"},{"key":"2025020923402245000_2025.01.03.631124v2.39","doi-asserted-by":"crossref","unstructured":"Constantinides MG , Link VM , Tamoutounour S , Wong AC , Perez-Chaparro PJ , Han SJ , Chen YE , Li K , Farhat S , Weckel A , et al: MAIT cells are imprinted by the microbiota in early life and promote tissue repair. Science 2019, 366.","DOI":"10.1126\/science.aax6624"},{"key":"2025020923402245000_2025.01.03.631124v2.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.07.039"},{"key":"2025020923402245000_2025.01.03.631124v2.41","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw2719"},{"key":"2025020923402245000_2025.01.03.631124v2.42","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj2829"},{"key":"2025020923402245000_2025.01.03.631124v2.43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1127588"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.01.03.631124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:48:23Z","timestamp":1768463303000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.01.03.631124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,3]]},"references-count":43,"URL":"https:\/\/doi.org\/10.1101\/2025.01.03.631124","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1186\/s12974-025-03413-7","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,1,3]]},"subtype":"preprint"}}