RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (30)
Hamsa Narasimhan
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Maria L. Richter
Biomedical Center, Physiological Chemistry, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Ramin Shakiba
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Nikos E. Papaioannou
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Christina Stehle
Institute for Medical Immunology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin
Kaushikk Ravi Rengarajan
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Isabel Ulmert
Section for Experimental and Translational Immunology, Institute for Health Technology, Technical University of Denmark
Arek Kendirli
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität in Munich
Clara de la Rosa
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität in Munich
Pin-Yu Kuo
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Abigail Altman
Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University
Philipp Münch
Institute for Molecular Medicine and Research Center for Immunotherapy (Forschungszentrum für Immuntherapie), University Medical Center Johannes Gutenberg-University Mainz
Saba Mahboubi
Institute for Molecular Medicine and Research Center for Immunotherapy (Forschungszentrum für Immuntherapie), University Medical Center Johannes Gutenberg-University Mainz
Vanessa Küntzel
Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Amina Sayed
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Eva-Lena Stange
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Jonas Pes
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Alina Ulezko Antonova
Department of Pathology and Immunology, Washington University School of Medicine
Carlos-Filipe Pereira
Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University
Ludger Klein
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich
Diana Dudziak
Institute of Immunology, Jena University Hospital of the Friedrich-Schiller-University
Marco Colonna
Natalia Torow
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Mathias W. Hornef
Institute of Medical Microbiology, Rheinisch-Westfälische Technische Hochschule Aachen University Hospital
Björn E. Clausen
Institute for Molecular Medicine and Research Center for Immunotherapy (Forschungszentrum Informatik), University Medical Center of the Johannes Gutenberg-University Mainz
Martin Kerschensteiner
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität in Munich
Katharina Lahl
Section for Experimental and Translational Immunology, Institute for Health Technology, Technical University of Denmark
Chiara Romagnani
Institute for Medical Immunology, Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin
Maria Colomé-Tatché
Barbara U. Schraml
Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität in Munich