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.

Czech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Department of Cell Biology Faculty of Science Charles University Prague Prague Czech Republic

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

Genomics Core Facility European Molecular Biology Laboratory Services and Technology Unit Heidelberg Germany

Helmholtz Zentrum München Institut für Allergieforschung Neuherberg Germany

Institute for Immunology Faculty of Medicine Ludwig Maximilans Universität Munich Germany

Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia

Laboratory of Genomics and Bioinformatics Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

Laboratory of Immunobiology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

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J Exp Med. 2019 May 6;216(5):1010-1011. doi: 10.1084/jem.20190246. PubMed

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