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Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses

Druzd, David
Matveeva, Olga
Ince, Louise
Harrison, Ute
He, Wenyan
Schmal, Christoph
Herzel, Hanspeter
Tsang, Anthony H
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Published in Immunity. 2017, vol. 46, no. 1, p. 120-132
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 Immunity/immunologyAdoptive TransferAnimalsChemotaxisLeukocyte/immunologyCircadian Clocks/immunologyEncephalomyelitisAutoimmuneExperimental/immunologyFlow CytometryFluorescent Antibody TechniqueImmunologic Surveillance/immunologyLymph Nodes/immunologyLymphocytes/immunologyMiceMiceInbred C57BLMiceTransgenicReal-Time Polymerase Chain Reaction
PMID: 28087238
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Research group Groupe Christoph Scheiermann (995)
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DRUZD, David et al. Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses. In: Immunity, 2017, vol. 46, n° 1, p. 120-132. doi: 10.1016/j.immuni.2016.12.011

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Deposited on : 2018-12-14

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