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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,7,25]]},"abstract":"<jats:p>\n                    Autoreactive encephalitogenic T cells exist in the healthy immune repertoire but need a trigger to induce CNS inflammation. The underlying mechanisms remain elusive, whereby microbiota were shown to be involved in the manifestation of CNS autoimmunity. Here, we used intravital imaging to explore how microbiota affect the T cells as trigger of CNS inflammation. Encephalitogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells transduced with the calcium-sensing protein Twitch-2B showed calcium signaling with higher frequency than polyclonal T cells in the small intestinal lamina propria (LP) but not in Peyer\u2019s patches. Interestingly, nonencephalitogenic T cells specific for OVA and LCMV also showed calcium signaling in the LP, indicating a general stimulating effect of microbiota. The observed calcium signaling was microbiota and MHC class II dependent as it was significantly reduced in germfree animals and after administration of anti-MHC class II antibody, respectively. As a consequence of T cell stimulation in the small intestine, the encephalitogenic T cells start expressing Th17-axis genes. Finally, we show the migration of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from the small intestine into the CNS. In summary, our direct in vivo visualization revealed that microbiota induced T cell activation in the LP, which directed T cells to adopt a Th17-like phenotype as a trigger of CNS inflammation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2302697120","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T13:38:06Z","timestamp":1689773886000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Visualizing the activation of encephalitogenic T cells in the ileal lamina propria by in vivo two-photon imaging"],"prefix":"10.1073","volume":"120","author":[{"given":"Isabel J.","family":"Bauer","sequence":"first","affiliation":[{"name":"Institute of Clinical Neuroimmunology, University Hospital, LMU Munich and Biomedical Center, Faculty of Medicine, Planegg-Martinsried 82152, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4379-3787","authenticated-orcid":false,"given":"Ping","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, University Hospital, LMU Munich and Biomedical Center, Faculty of Medicine, Planegg-Martinsried 82152, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-3968","authenticated-orcid":false,"given":"Katrin F.","family":"L\u00e4mmle","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, University Hospital, LMU Munich and Biomedical Center, Faculty of Medicine, Planegg-Martinsried 82152, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5057-1923","authenticated-orcid":false,"given":"Sofia","family":"Tyystj\u00e4rvi","sequence":"additional","affiliation":[{"name":"Institute for Experimental Neuroimmunology, Technical University of Munich School of Medicine, Munich 81675, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Alterauge","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Planegg-Martinsried 82152, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-8288","authenticated-orcid":false,"given":"Dirk","family":"Baumjohann","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Planegg-Martinsried 82152, Germany"},{"name":"Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn 53127, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsup","family":"Yoon","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, University Hospital, LMU Munich and Biomedical Center, Faculty of Medicine, Planegg-Martinsried 82152, Germany"},{"name":"Neuroimmunology group, Max Planck Institute of Neurobiology, Planegg-Martinsried 82152, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3633-0955","authenticated-orcid":false,"given":"Thomas","family":"Korn","sequence":"additional","affiliation":[{"name":"Institute for Experimental Neuroimmunology, Technical University of Munich School of Medicine, Munich 81675, Germany"},{"name":"Munich Cluster for Systems Neurology, Munich 81377, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Wekerle","sequence":"additional","affiliation":[{"name":"Institute of Clinical Neuroimmunology, University 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Fang \u201cVisualizing the stimulation of encephalitogenic T cells in gut associated lymphoid tissue as a trigger of autoimmunity\u201d PhD Dissertation LMU Munich (2018)."},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10228"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2015.03.020"},{"key":"e_1_3_4_54_2","unstructured":"N. Kawakami Transcriptome analysis of CD4+ T cells emigrating from gut. Sequence Read Archive (SRA). https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/986071. Deposited 21 June 2023."},{"key":"e_1_3_4_55_2","unstructured":"N. Kawakami SAMN35818795\/ Transcriptome analysis of CD4+ T cells emigrating from gut. Sequence Read Archive (SRA). https:\/\/www.ncbi.nlm.nih.gov\/sra\/?term=SAMN35818795. Accessed 21 June 2023."},{"key":"e_1_3_4_56_2","unstructured":"N. Kawakami SAMN35818796\/ Transcriptome analysis of CD4+ T cells emigrating from gut. 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