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 Dibner; Henrik Oster; Jörg Renkawitz; Christoph Scheiermann

doi:10.1038/s41590-021-01040-x

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

Institute of Neurobiology

30 Citations (Scopus)

Abstract

Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses^1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood^3,4. 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 language	English
Journal	Nature Immunology
Volume	22
Issue number	11
Pages (from-to)	1375-1381
Number of pages	7
ISSN	1529-2908
DOIs	https://doi.org/10.1038/s41590-021-01040-x
Publication status	Published - 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

2.22-17 Endocrinology, Diabetology, Metabolism
2.22-19 Dermatology
2.21-05 Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41590-021-01040-x

Cite this

Holtkamp, S. J., Ince, L. M., Barnoud, C., Schmitt, M. T., Sinturel, F., Pilorz, V., Pick, R., Jemelin, S., Mühlstädt, M., Boehncke, W. H., Weber, J., Laubender, D., Philippou-Massier, J., Chen, C. S., Holtermann, L., Vestweber, D., Sperandio, M., Schraml, B. U., Halin, C., ... Scheiermann, C. (2021). Circadian clocks guide dendritic cells into skin lymphatics. Nature Immunology, 22(11), 1375-1381. https://doi.org/10.1038/s41590-021-01040-x

@article{40d12a2437d74f9eb8beb6f6e707c741,

title = "Circadian clocks guide dendritic cells into skin lymphatics",

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.",

author = "Holtkamp, {Stephan J.} and Ince, {Louise M.} and Coline Barnoud and Schmitt, {Madeleine T.} and Flore Sinturel and Violetta Pilorz and Robert Pick and St{\'e}phane Jemelin and Michael M{\"u}hlst{\"a}dt and Boehncke, {Wolf Henning} and Jasmin Weber and David Laubender and Julia Philippou-Massier and Chen, {Chien Sin} and Leonie Holtermann and Dietmar Vestweber and Markus Sperandio and Schraml, {Barbara U.} and Cornelia Halin and Charna Dibner and Henrik Oster and J{\"o}rg Renkawitz and Christoph Scheiermann",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = nov,

doi = "10.1038/s41590-021-01040-x",

language = "English",

volume = "22",

pages = "1375--1381",

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Holtkamp, SJ, Ince, LM, Barnoud, C, Schmitt, MT, Sinturel, F, Pilorz, V, Pick, R, Jemelin, S, Mühlstädt, M, Boehncke, WH, Weber, J, Laubender, D, Philippou-Massier, J, Chen, CS, Holtermann, L, Vestweber, D, Sperandio, M, Schraml, BU, Halin, C, Dibner, C, Oster, H, Renkawitz, J & Scheiermann, C 2021, 'Circadian clocks guide dendritic cells into skin lymphatics', Nature Immunology, vol. 22, no. 11, pp. 1375-1381. https://doi.org/10.1038/s41590-021-01040-x

TY - JOUR

T1 - Circadian clocks guide dendritic cells into skin lymphatics

AU - Holtkamp, Stephan J.

AU - Ince, Louise M.

AU - Barnoud, Coline

AU - Schmitt, Madeleine T.

AU - Sinturel, Flore

AU - Pilorz, Violetta

AU - Pick, Robert

AU - Jemelin, Stéphane

AU - Mühlstädt, Michael

AU - Boehncke, Wolf Henning

AU - Weber, Jasmin

AU - Laubender, David

AU - Philippou-Massier, Julia

AU - Chen, Chien Sin

AU - Holtermann, Leonie

AU - Vestweber, Dietmar

AU - Sperandio, Markus

AU - Schraml, Barbara U.

AU - Halin, Cornelia

AU - Dibner, Charna

AU - Oster, Henrik

AU - Renkawitz, Jörg

AU - Scheiermann, Christoph

PY - 2021/11

Y1 - 2021/11

N2 - 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.

AB - 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.

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DO - 10.1038/s41590-021-01040-x

M3 - Journal articles

C2 - 34663979

AN - SCOPUS:85117202724

SN - 1529-2908

VL - 22

SP - 1375

EP - 1381

JO - Nature Immunology

JF - Nature Immunology

IS - 11

ER -

Circadian clocks guide dendritic cells into skin lymphatics

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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