TY - JOUR
T1 - Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses
AU - Druzd, David
AU - Matveeva, Olga
AU - Ince, Louise
AU - Harrison, Ute
AU - He, Wenyan
AU - Schmal, Christoph
AU - Herzel, Hanspeter
AU - Tsang, Anthony H.
AU - Kawakami, Naoto
AU - Leliavski, Alexei
AU - Uhl, Olaf
AU - Yao, Ling
AU - Sander, Leif Erik
AU - Chen, Chien Sin
AU - Kraus, Kerstin
AU - de Juan, Alba
AU - Hergenhan, Sophia Martina
AU - Ehlers, Marc
AU - Koletzko, Berthold
AU - Haas, Rainer
AU - Solbach, Werner
AU - Oster, Henrik
AU - Scheiermann, Christoph
PY - 2017/1/17
Y1 - 2017/1/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85009275180&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2016.12.011
DO - 10.1016/j.immuni.2016.12.011
M3 - Journal articles
C2 - 28087238
AN - SCOPUS:85009275180
SN - 1074-7613
VL - 46
SP - 120
EP - 132
JO - Immunity
JF - Immunity
IS - 1
ER -