Circadian clocks guide dendritic cells into skin lymphatics

Stephan J. Holtkamp, Louise M. Ince, Coline Barnoud, Madeleine T. Schmitt, Flore Sinturel, Violetta Pilorz, Robert Pick, Stéphane Jemelin, Michael Mühlstädt, Wolf Henning Boehncke, Jasmin Weber, David Laubender, Julia Philippou-Massier, Chien Sin Chen, Leonie Holtermann, Dietmar Vestweber, Markus Sperandio, Barbara U. Schraml, Cornelia Halin, Charna DibnerHenrik Oster, Jörg Renkawitz, Christoph Scheiermann*

*Corresponding author for this work
30 Citations (Scopus)

Abstract

Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood3,4. Here, we demonstrate that dendritic cells (DCs) have a circadian migration pattern into LVs, which peaks during the rest phase in mice. This migration pattern is determined by rhythmic gradients in the expression of the chemokine CCL21 and of adhesion molecules in both mice and humans. Chronopharmacological targeting of the involved factors abrogates circadian migration of DCs. We identify cell-intrinsic circadian oscillations in skin lymphatic endothelial cells (LECs) and DCs that cogovern these rhythms, as their genetic disruption in either cell type ablates circadian trafficking. These observations indicate that circadian clocks control the infiltration of DCs into skin lymphatics, a process that is essential for many adaptive immune responses and relevant for vaccination and immunotherapies.

Original languageEnglish
JournalNature Immunology
Volume22
Issue number11
Pages (from-to)1375-1381
Number of pages7
ISSN1529-2908
DOIs
Publication statusPublished - 11.2021

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Center for Research on Inflammation of the Skin (CRIS)
  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

  • 205-17 Endocrinology, Diabetology, Metabolism
  • 205-19 Dermatology
  • 204-05 Immunology

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