Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses

David Druzd, Olga Matveeva, Louise Ince, Ute Harrison, Wenyan He, Christoph Schmal, Hanspeter Herzel, Anthony H. Tsang, Naoto Kawakami, Alexei Leliavski, Olaf Uhl, Ling Yao, Leif Erik Sander, Chien Sin Chen, Kerstin Kraus, Alba de Juan, Sophia Martina Hergenhan, Marc Ehlers, Berthold Koletzko, Rainer HaasWerner Solbach, Henrik Oster, Christoph Scheiermann*

*Korrespondierende/r Autor/-in für diese Arbeit
9 Zitate (Scopus)

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.

OriginalspracheEnglisch
ZeitschriftImmunity
Jahrgang46
Ausgabenummer1
Seiten (von - bis)120-132
Seitenumfang13
ISSN1074-7613
DOIs
PublikationsstatusVeröffentlicht - 17.01.2017

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)
  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

DFG-Fachsystematik

  • 204-05 Immunologie
  • 205-04 Physiologie
  • 205-22 Klinische Immunologie und Allergologie

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