Visualizing the activation of encephalitogenic T cells in the ileal lamina propria by in vivo two- photon imaging

Bauer, Isabel J.; Fang, Ping; Lammle, Katrin F.; Tyystjarvi, Sofia; Alterauge, Dominik; Baumjohann, Dirk; Yoon, Hongsup; Korn, Thomas; Wekerle, Hartmut und Kawakami, Naoto (2023): Visualizing the activation of encephalitogenic T cells in the ileal lamina propria by in vivo two- photon imaging. In: Proceedings of the National Academy of Sciences of the United States of America, Bd. 120, Nr. 30, e2302697120

Abstract

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 autoim-munity. Here, we used intravital imaging to explore how microbiota affect the T cells as trigger of CNS inflammation. Encephalitogenic CD4(+) 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's 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(+) 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198