Progressive changes in phenotype, transcriptome and proliferation capacity characterise continued maturation and migration of intestinal cDCs in homeostasis

Nature Communications, vol. 16, pp. 8204

Abstract

Conventional dendritic cells (cDCs) are important antigen presenting cells which link innate and adaptive immunity by transferring antigenic information from peripheral organs to T cells in lymph nodes (LNs). However, despite their central function in the induction of adaptive immune responses, the kinetics and molecular regulation of the cDC life cycle and migration remain poorly understood. Using a variety of in vivo techniques, we examine the kinetics of cDC turnover in the intestine and address the molecular changes throughout the various stages of the cDC life cycle - from tissue entry and differentiation to CCR7 upregulation and subsequent migration into draining LNs. Our data demonstrate that the life cycle of gut cDCs is highly dynamic, characterised by continuous alterations in transcriptome, protein expression and proliferation rates. These progressive changes culminate in cDC homeostatic activation and migration resulting in a resource-intensive daily turnover of up to a quarter of intestinal cDCs and an almost complete daily replacement of the migratory cDC compartment in the mesenteric LN. This high turnover rate ensures that the mesenteric LN maintains an accurate reflection of the intestinal immunological state, supporting rapid adaptation to emerging immune challenges.

Authors 14

1. Fabian Tobias Hager Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

2. Tran Nguyen Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

3. Lydia Kopplin Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

4. Anna T. Andrusaite

   University of Glasgow

   Affiliation as printed

   School of Infection and Immunity, University of Glasgow, Glasgow, UK

5. Susan A. V. Jennings Aachen Functional Microbiome Research Group Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany

6. Britta Simons Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

7. Andrea Leufgen Aachen Institute of Molecular Medicine

   RWTH Aachen University

   Affiliation as printed

   Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

8. Thomas Clavel Aachen Functional Microbiome Research Group Institute of Medical Microbiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Functional Microbiome Research Group, Institute of Medical Microbiology, University Hospital of RWTH Aachen, Aachen, Germany

9. Simon W. F. Milling

   University of Glasgow

   Affiliation as printed

   School of Infection and Immunity, University of Glasgow, Glasgow, UK

10. Immo Prinz

    Medizinische Hochschule Hannover · University Medical Center Hamburg-Eppendorf

    Affiliation as printed

    Institute of Immunology, Hannover Medical School, Hannover, Germany

    Institute of Systems Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

11. Reinhold Förster

    Medizinische Hochschule Hannover

    Affiliation as printed

    Institute of Immunology, Hannover Medical School, Hannover, Germany

12. Thomas Stiehl Aachen Institute for Computational Biomedicine and Disease modelling with focus on phase transitions between phenotypes

    RWTH Aachen University

    Affiliation as printed

    Institute for Computational Biomedicine and Disease modelling with focus on phase transitions between phenotypes, RWTH Aachen University, Aachen, Germany

13. Oliver Pabst Aachen Institute of Molecular Medicine

    RWTH Aachen University

    Affiliation as printed

    Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany

14. Vuk Cerovic corresponding Aachen Institute of Molecular Medicine

    RWTH Aachen University

    Affiliation as printed

    Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany. vcerovic@ukaachen.de

    Institute of Molecular Medicine, RWTH Aachen University, Aachen, Germany