RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells
Proceedings of the National Academy of Sciences, vol. 122, pp. e2417308122
Abstract
Conventional dendritic cells (cDCs) are potent antigen-presenting cells (APCs) that integrate signals from their environment allowing them to direct situation-adapted immunity. Thereby they harbor great potential for being targeted in vaccination, autoimmunity, and cancer. Here, we use fate mapping, functional analyses, and comparative cross-species transcriptomics to show that RORγt + DCs are a conserved, functionally versatile, and transcriptionally distinct type of DCs. RORγt + DCs entail various populations described in different contexts including Janus cells/RORγt-expressing extrathymic Aire-expressing cells (eTACs), subtypes of Thetis cells, RORγt + -DC (R-DC) like cells, cDC2C and ACY3 + DCs. We show that in response to inflammatory triggers, RORγt + DCs can migrate to lymph nodes and in the spleen can activate naïve CD4 + T cells. These findings expand the functional repertoire of RORγt + DCs beyond the known role of eTACs and Thetis cells in inducing T cell tolerance to self-antigens and intestinal microbes in mice. We further show that RORγt + DCs with proinflammatory features accumulate in autoimmune neuroinflammation in mice and men. Thus, our work establishes RORγt + DCs as immune sentinel cells that exhibit a broad functional spectrum ranging from inducing peripheral T cell tolerance to T cell activation depending on signals they integrate from their environment.
Authors 29
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Institut für Immunologie · Institut für Kardiovaskuläre Physiologie und Pathophysiologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Physiological Chemistry, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Institut für Immunologie · Institut für Kardiovaskuläre Physiologie und Pathophysiologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Institut für Kardiovaskuläre Physiologie und Pathophysiologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Institute for Medical Immunology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin
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Institut für Immunologie · Institut für Kardiovaskuläre Physiologie und Pathophysiologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Technical University of Denmark
Affiliation as printed
Section for Experimental and Translational Immunology, Institute for Health Technology, Technical University of Denmark
Section for Experimental and Translational Immunology, Institute for Health Technology, Technical University of Denmark, Kongens Lyngby 2800, Denmark
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Munich Cluster for Systems Neurology · Institut für Klinische Neuroimmunologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Medical Faculty, Ludwig-Maximilians-Universität in Munich
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität in Munich
Munich Cluster of Systems Neurology (SyNergy)
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Institut für Klinische Neuroimmunologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Medical Faculty, Ludwig-Maximilians-Universität in Munich
Graduate School of Systemic Neurosciences, LMU
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität in Munich
Graduate School of Systemic Neurosciences, LMU, Planegg-Martinsried 82152, Germany
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Institut für Immunologie · Institut für Kardiovaskuläre Physiologie und Pathophysiologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Affiliation as printed
Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University
Wallenberg Centre for Molecular Medicine at Lund University
Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, Lund 221 84, Sweden
Wallenberg Centre for Molecular Medicine at Lund University, Lund 221 84, Sweden
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Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
Institute for Molecular Medicine and Research Center for Immunotherapy (Forschungszentrum für Immuntherapie), University Medical Center Johannes Gutenberg-University Mainz
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Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
Institute for Molecular Medicine and Research Center for Immunotherapy (Forschungszentrum für Immuntherapie), University Medical Center Johannes Gutenberg-University Mainz
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Institut für Kardiovaskuläre Physiologie und Pathophysiologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
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Washington University in St. Louis
Affiliation as printed
Department of Pathology and Immunology, Washington University School of Medicine
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110
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Affiliation as printed
Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University
Wallenberg Centre for Molecular Medicine at Lund University
Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, Lund 221 84, Sweden
Wallenberg Centre for Molecular Medicine at Lund University, Lund 221 84, Sweden
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Institut für Immunologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Jena University Hospital · Friedrich Schiller University Jena
Affiliation as printed
Institute of Immunology, Jena University Hospital of the Friedrich-Schiller-University
Institute of Immunology, Jena University Hospital of the Friedrich-Schiller-University, Jena 07747, Germany
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Washington University in St. Louis
Affiliation as printed
Department of Pathology and Immunology, Washington University School of Medicine
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
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Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
Institute for Molecular Medicine and Research Center for Immunotherapy (Forschungszentrum für Immuntherapie), University Medical Center Johannes Gutenberg-University Mainz
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Munich Cluster for Systems Neurology · Institut für Klinische Neuroimmunologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Medical Faculty, Ludwig-Maximilians-Universität in Munich
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität in Munich
Munich Cluster of Systems Neurology (SyNergy)
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University of Calgary · Lund University · Technical University of Denmark
Affiliation as printed
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary
Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary
Immunology Section, Lund University
Section for Experimental and Translational Immunology, Institute for Health Technology, Technical University of Denmark
Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB T2N 1N4, Canada
Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
Immunology Section, Lund University, Lund 221 84, Sweden
Section for Experimental and Translational Immunology, Institute for Health Technology, Technical University of Denmark, Kongens Lyngby 2800, Denmark
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Humboldt-Universität zu Berlin · Freie Universität Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Institute for Medical Immunology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin
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Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Physiological Chemistry, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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Barbara U. Schraml corresponding
Institut für Immunologie · Institut für Kardiovaskuläre Physiologie und Pathophysiologie · Ludwig-Maximilians-Universität München
Affiliation as printed
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
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