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Immunity. 2017 Jan 17;46(1):120-132. doi: 10.1016/j.immuni.2016.12.011. Epub 2017 Jan 10.

Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses.

Author information

1
BioMedical Center, Walter-Brendel-Centre for Experimental Medicine, Ludwig-Maximilians-University, 82152 Planegg-Martinsried, Germany.
2
Medical Department I, University of Lübeck, 23562 Lübeck, Germany.
3
Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians-University, 80336 Munich, Germany.
4
Charité University Hospital Berlin, 10117 Berlin, Germany.
5
Institute for Theoretical Biology, Humboldt University of Berlin, 10115 Berlin, Germany.
6
BioMedical Center, Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, 82152 Planegg-Martinsried, Germany.
7
Laboratory of Immunology, Institute for Nutrition Medicine, University of Lübeck, 23562 Lübeck, Germany.
8
Ludwig-Maximilians-University, Dr. von Hauner Children's Hospital, University of Munich Medical Center, 80337 Munich, Germany.
9
Department of Infectious Diseases and Pulmonary Medicine, Charité University Hospital Berlin, 10117 Berlin, Germany.
10
Center for Infection and Inflammation, University of Lübeck, 23562 Lübeck, Germany.
11
BioMedical Center, Walter-Brendel-Centre for Experimental Medicine, Ludwig-Maximilians-University, 82152 Planegg-Martinsried, Germany. Electronic address: christoph.scheiermann@med.uni-muenchen.de.

Abstract

Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes. Dendritic cell numbers peaked in phase with lymphocytes, with diurnal oscillations being present in disease severity after immunization to induce experimental autoimmune encephalomyelitis (EAE). These rhythms were abolished by genetic disruption of T cell clocks, demonstrating a circadian regulation of lymphocyte migration through lymph nodes with time-of-day of immunization being critical for adaptive immune responses weeks later.

KEYWORDS:

adaptive immune response; circadian rhythm; immunization; leukocyte trafficking; lymph node egress; lymph node homing

PMID:
28087238
PMCID:
PMC5263259
DOI:
10.1016/j.immuni.2016.12.011
[Indexed for MEDLINE]
Free PMC Article

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