Group 3 Innate Lymphoid Cells Program a Distinct Subset of IL-22BP-Producing Dendritic Cells Demarcating Solitary Intestinal Lymphoid Tissues

Fabian Guendel; Michael Kofoed-Branzk; Konrad Gronke; Caroline Tizian; Mario Witkowski; Hung-Wei Cheng; Gitta Anne Heinz; Frederik Heinrich; Pawel Durek; Paula S Norris; Carl F Ware; Christiane Ruedl; Susanne Herold; Klaus Pfeffer; Thomas Hehlgans; Ari Waisman; Burkhard Becher; Anastasios D Giannou; Sebastian Brachs; Karolina Ebert; Yakup Tanriver; Burkhard Ludewig; Mir-Farzin Mashreghi; Andrey A Kruglov; Andreas Diefenbach

doi:10.1016/j.immuni.2020.10.012

Group 3 Innate Lymphoid Cells Program a Distinct Subset of IL-22BP-Producing Dendritic Cells Demarcating Solitary Intestinal Lymphoid Tissues

Immunity. 2020 Nov 17;53(5):1015-1032.e8. doi: 10.1016/j.immuni.2020.10.012.

Authors

Fabian Guendel¹, Michael Kofoed-Branzk¹, Konrad Gronke¹, Caroline Tizian¹, Mario Witkowski¹, Hung-Wei Cheng², Gitta Anne Heinz³, Frederik Heinrich³, Pawel Durek³, Paula S Norris⁴, Carl F Ware⁴, Christiane Ruedl⁵, Susanne Herold⁶, Klaus Pfeffer⁷, Thomas Hehlgans⁸, Ari Waisman⁹, Burkhard Becher¹⁰, Anastasios D Giannou¹¹, Sebastian Brachs¹², Karolina Ebert¹³, Yakup Tanriver¹⁴, Burkhard Ludewig¹⁵, Mir-Farzin Mashreghi¹⁶, Andrey A Kruglov¹⁷, Andreas Diefenbach¹⁸

Affiliations

¹ Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch Strasse 2, 10117 Berlin, Germany; Mucosal and Developmental Immunology, Deutsches Rheuma-Forschungszentrum (DRFZ), an institute of the Leibniz Association, 10117 Berlin, Germany.
² Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
³ Therapeutic Gene Regulation, Deutsches Rheuma-Forschungszentrum (DRFZ), an institute of the Leibniz Association, 10117 Berlin, Germany.
⁴ Laboratory of Molecular Immunology, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
⁵ School of Biological Sciences, Nanyang Technological University Singapore, Singapore.
⁶ Department of Internal Medicine II, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research (DZL), Giessen, Germany.
⁷ Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
⁸ Regensburg Center for Interventional Immunology (RCI), Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany; Chair for Immunology, Regensburg University, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
⁹ Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
¹⁰ Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
¹¹ Section of Molecular Immunology und Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
¹² Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany; Center for Cardiovascular Research (CCR), Charité-Universitätsmedizin Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany.
¹³ Institute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹⁴ Institute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Internal Medicine IV, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹⁵ Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
¹⁶ Therapeutic Gene Regulation, Deutsches Rheuma-Forschungszentrum (DRFZ), an institute of the Leibniz Association, 10117 Berlin, Germany; BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁷ Microbiota and Chronic Inflammation, Deutsches Rheuma-Forschungszentrum (DRFZ), an institute of the Leibniz Association, 10117 Berlin, Germany; Belozersky Institute of Physico-Chemical Biology and Biological Faculty, M.V. Lomonosov Moscow State University, Moscow 119234, Russia; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
¹⁸ Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; Berlin Institute of Health (BIH), Anna-Louisa-Karsch Strasse 2, 10117 Berlin, Germany; Mucosal and Developmental Immunology, Deutsches Rheuma-Forschungszentrum (DRFZ), an institute of the Leibniz Association, 10117 Berlin, Germany. Electronic address: andreas.diefenbach@charite.de.

PMID: 33207209
DOI: 10.1016/j.immuni.2020.10.012

Abstract

Solitary intestinal lymphoid tissues such as cryptopatches (CPs) and isolated lymphoid follicles (ILFs) constitute steady-state activation hubs containing group 3 innate lymphoid cells (ILC3) that continuously produce interleukin (IL)-22. The outer surface of CPs and ILFs is demarcated by a poorly characterized population of CD11c⁺ cells. Using genome-wide single-cell transcriptional profiling of intestinal mononuclear phagocytes and multidimensional flow cytometry, we found that CP- and ILF-associated CD11c⁺ cells were a transcriptionally distinct subset of intestinal cDCs, which we term CIA-DCs. CIA-DCs required programming by CP- and ILF-resident CCR6⁺ ILC3 via lymphotoxin-β receptor signaling in cDCs. CIA-DCs differentially expressed genes associated with immunoregulation and were the major cellular source of IL-22 binding protein (IL-22BP) at steady state. Mice lacking CIA-DC-derived IL-22BP exhibited diminished expression of epithelial lipid transporters, reduced lipid resorption, and changes in body fat homeostasis. Our findings provide insight into the design principles of an immunoregulatory checkpoint controlling nutrient absorption.

Keywords: cryptopatches; dendritic cells; innate lymphoid cells; interleukin 22 binding protein; isolated lymphoid follicles; solitary intestinal lymphoid tissues.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
Dendritic Cells / immunology*
Dendritic Cells / metabolism*
Gene Expression
Gene Expression Profiling
Gene Expression Regulation
Immunity, Innate*
Immunophenotyping
Intestinal Mucosa / immunology
Intestinal Mucosa / metabolism
Lipid Metabolism
Lymphocyte Subsets / immunology*
Lymphocyte Subsets / metabolism*
Mice
Mice, Transgenic
Peyer's Patches / cytology*
Peyer's Patches / immunology*
RNA, Small Cytoplasmic / genetics
Receptors, Interleukin / biosynthesis*
Receptors, Interleukin / genetics
Signal Transduction

Substances

Biomarkers
RNA, Small Cytoplasmic
Receptors, Interleukin
interleukin-22 receptor