Circadian clocks guide dendritic cells into skin lymphatics
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...
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| Published in | Nature immunology Vol. 22; no. 11; pp. 1375 - 1381 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Nature Publishing Group US
01.11.2021
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1529-2908 1529-2916 1529-2916 |
| DOI | 10.1038/s41590-021-01040-x |
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| 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.
Scheiermann and colleagues show that circadian clocks control the infiltration of dendritic cells into skin lymphatics in mice and humans, with a peak migration to the lymph nodes during the rest phase. |
|---|---|
| AbstractList | 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. Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses.sup.1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood.sup.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. Scheiermann and colleagues show that circadian clocks control the infiltration of dendritic cells into skin lymphatics in mice and humans, with a peak migration to the lymph nodes during the rest phase. 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. Scheiermann and colleagues show that circadian clocks control the infiltration of dendritic cells into skin lymphatics in mice and humans, with a peak migration to the lymph nodes during the rest phase. 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.Scheiermann and colleagues show that circadian clocks control the infiltration of dendritic cells into skin lymphatics in mice and humans, with a peak migration to the lymph nodes during the rest phase. 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.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. Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses.sup.1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood.sup.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. Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses . Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood . 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. |
| Audience | Academic |
| Author | Weber, Jasmin Boehncke, Wolf-Henning Ince, Louise M. Schmitt, Madeleine T. Scheiermann, Christoph Schraml, Barbara U. Barnoud, Coline Mühlstädt, Michael Dibner, Charna Halin, Cornelia Renkawitz, Jörg Chen, Chien-Sin Sinturel, Flore Pick, Robert Vestweber, Dietmar Sperandio, Markus Holtermann, Leonie Philippou-Massier, Julia Jemelin, Stéphane Laubender, David Pilorz, Violetta Holtkamp, Stephan J. Oster, Henrik |
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Institute for Molecular Biomedicine – sequence: 17 givenname: Markus orcidid: 0000-0002-7689-3613 surname: Sperandio fullname: Sperandio, Markus organization: Biomedical Center (BMC), Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine (WBex), Faculty of Medicine, Ludwig-Maximilians-Universität Munich – sequence: 18 givenname: Barbara U. orcidid: 0000-0002-5801-0151 surname: Schraml fullname: Schraml, Barbara U. organization: Biomedical Center (BMC), Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine (WBex), Faculty of Medicine, Ludwig-Maximilians-Universität Munich – sequence: 19 givenname: Cornelia orcidid: 0000-0002-7899-2850 surname: Halin fullname: Halin, Cornelia organization: Institute of Pharmaceutical Sciences, ETH Zurich – sequence: 20 givenname: Charna surname: Dibner fullname: Dibner, Charna organization: Department of Medicine, Division of Endocrinology, Diabetes, Nutrition and Patient Education, University Hospitals of Geneva, Department of Cell Physiology and Metabolism, University of Geneva, Diabetes Center, Faculty of Medicine, University of Geneva, Institute of Genetics and Genomics of Geneva (iGE3), University of Geneva – sequence: 21 givenname: Henrik surname: Oster fullname: Oster, Henrik organization: Institute of Neurobiology, University of Lübeck – sequence: 22 givenname: Jörg orcidid: 0000-0003-2856-3369 surname: Renkawitz fullname: Renkawitz, Jörg organization: Biomedical Center (BMC), Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine (WBex), Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Laboratory ‘Cell Biology of the Immune System’, Biomedical Center (BMC), Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine (WBex), Faculty of Medicine, Ludwig-Maximilians-Universität Munich – sequence: 23 givenname: Christoph orcidid: 0000-0002-9212-0995 surname: Scheiermann fullname: Scheiermann, Christoph email: christoph.scheiermann@unige.ch organization: Biomedical Center (BMC), Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine (WBex), Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34663979$$D View this record in MEDLINE/PubMed |
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| Snippet | Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses
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. Circadian... Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses 1,2 . Circadian... Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses . Circadian rhythms... Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses.sup.1,2. Circadian... Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses1,2. Circadian rhythms... |
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| SubjectTerms | 631/250/1617/2069 631/250/2152 Adaptive Immunity Aged Animals Biomedical and Life Sciences Biomedicine CCL21 protein Cell Adhesion Molecules - genetics Cell Adhesion Molecules - metabolism Cells Cells, Cultured Chemokine CCL21 - genetics Chemokine CCL21 - metabolism Chemokines Chemotaxis Circadian Clocks Circadian rhythm Circadian Rhythm Signaling Peptides and Proteins - genetics Circadian Rhythm Signaling Peptides and Proteins - metabolism Circadian rhythms Dendritic cells Dendritic Cells - immunology Dendritic Cells - metabolism Endothelial cells Female Health aspects Humans Immunological research Immunology Immunotherapy Infectious Diseases Infiltration Letter Leukocyte migration Lymph nodes Lymph Nodes - immunology Lymph Nodes - metabolism Lymphatic system Lymphatic Vessels - immunology Lymphatic Vessels - metabolism Male Mice Mice, Inbred C57BL Mice, Transgenic Motility Oscillations Physiological aspects Sensory neurons Skin Skin - immunology Skin - metabolism Time Factors Vaccination |
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| Title | Circadian clocks guide dendritic cells into skin lymphatics |
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