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Aire-expressing ILC3-like cells in the lymph node display potent APC features

T. Yamano, J. Dobeš, M. Vobořil, M. Steinert, T. Brabec, N. Ziętara, M. Dobešová, C. Ohnmacht, M. Laan, P. Peterson, V. Benes, R. Sedláček, R. Hanayama, M. Kolář, L. Klein, D. Filipp,

. 2019 ; 216 (5) : 1027-1037. [pub] 20190327

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20023953

The autoimmune regulator (Aire) serves an essential function for T cell tolerance by promoting the "promiscuous" expression of tissue antigens in thymic epithelial cells. Aire is also detected in rare cells in peripheral lymphoid organs, but the identity of these cells is poorly understood. Here, we report that Aire protein-expressing cells in lymph nodes exhibit typical group 3 innate lymphoid cell (ILC3) characteristics such as lymphoid morphology, absence of "classical" hematopoietic lineage markers, and dependence on RORγt. Aire+ cells are more frequent among lineage-negative RORγt+ cells of peripheral lymph nodes as compared with mucosa-draining lymph nodes, display a unique Aire-dependent transcriptional signature, express high surface levels of MHCII and costimulatory molecules, and efficiently present an endogenously expressed model antigen to CD4+ T cells. These findings define a novel type of ILC3-like cells with potent APC features, suggesting that these cells serve a function in the control of T cell responses.

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$a The autoimmune regulator (Aire) serves an essential function for T cell tolerance by promoting the "promiscuous" expression of tissue antigens in thymic epithelial cells. Aire is also detected in rare cells in peripheral lymphoid organs, but the identity of these cells is poorly understood. Here, we report that Aire protein-expressing cells in lymph nodes exhibit typical group 3 innate lymphoid cell (ILC3) characteristics such as lymphoid morphology, absence of "classical" hematopoietic lineage markers, and dependence on RORγt. Aire+ cells are more frequent among lineage-negative RORγt+ cells of peripheral lymph nodes as compared with mucosa-draining lymph nodes, display a unique Aire-dependent transcriptional signature, express high surface levels of MHCII and costimulatory molecules, and efficiently present an endogenously expressed model antigen to CD4+ T cells. These findings define a novel type of ILC3-like cells with potent APC features, suggesting that these cells serve a function in the control of T cell responses.
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$a Dobeš, Jan $u Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic. Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
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$a Vobořil, Matouš $u Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
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$a Steinert, Madlen $u Institute for Immunology, Faculty of Medicine, Ludwig-Maximilans-Universität, Munich, Germany.
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$a Brabec, Tomáš $u Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
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$a Ziętara, Natalia $u Institute for Immunology, Faculty of Medicine, Ludwig-Maximilans-Universität, Munich, Germany.
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$a Ohnmacht, Caspar $u Helmholtz Zentrum München, Institut für Allergieforschung, Neuherberg, Germany.
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$a Laan, Martti $u Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
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$a Peterson, Part $u Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
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$a Benes, Vladimir $u Genomics Core Facility, European Molecular Biology Laboratory, Services and Technology Unit, Heidelberg, Germany.
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$a Hanayama, Rikinari $u Department of Immunology, Kanazawa University Graduate School of Medical Sciences, and World Premier International Research Center Initiative Nano Life Science Institute, Kanazawa University, Ishikawa, Japan.
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$a Kolář, Michal $u Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
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$a Klein, Ludger $u Institute for Immunology, Faculty of Medicine, Ludwig-Maximilans-Universität, Munich, Germany ludger.klein@med.lmu.de.
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