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

Fabian T. Hager, Trong Hieu Nguyen, Asmae Laouina, Lydia Kopplin, Anna Andrusaite, Susan A. V. Jennings, Britta Simons, Andrea Leufgen, Thomas Clavel, Simon Milling, Immo Prinz, Reinhold Förster, Thomas Stiehl, Oliver Pabst and Vuk Cerovic ()
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Fabian T. Hager: RWTH Aachen University
Trong Hieu Nguyen: RWTH Aachen University
Asmae Laouina: RWTH Aachen University
Lydia Kopplin: RWTH Aachen University
Anna Andrusaite: University of Glasgow
Susan A. V. Jennings: University Hospital of RWTH Aachen
Britta Simons: RWTH Aachen University
Andrea Leufgen: RWTH Aachen University
Thomas Clavel: University Hospital of RWTH Aachen
Simon Milling: University of Glasgow
Immo Prinz: Hannover Medical School
Reinhold Förster: Hannover Medical School
Thomas Stiehl: RWTH Aachen University
Oliver Pabst: RWTH Aachen University
Vuk Cerovic: RWTH Aachen University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63559-z

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