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 Haas; Werner Solbach; Henrik Oster; Christoph Scheiermann

doi:10.1016/j.immuni.2016.12.011

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^*

^*Corresponding author for this work

9 Citations (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.

Original language	English
Journal	Immunity
Volume	46
Issue number	1
Pages (from-to)	120-132
Number of pages	13
ISSN	1074-7613
DOIs	https://doi.org/10.1016/j.immuni.2016.12.011
Publication status	Published - 17.01.2017

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

204-05 Immunology
205-04 Physiology
205-22 Clinical Immunology and Allergology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.immuni.2016.12.011

Cite this

Druzd, D., Matveeva, O., Ince, L., Harrison, U., He, W., Schmal, C., Herzel, H., Tsang, A. H., Kawakami, N., Leliavski, A., Uhl, O., Yao, L., Sander, L. E., Chen, C. S., Kraus, K., de Juan, A., Hergenhan, S. M., Ehlers, M., Koletzko, B., ... Scheiermann, C. (2017). Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses. Immunity, 46(1), 120-132. https://doi.org/10.1016/j.immuni.2016.12.011

@article{75dbcf8b174e4655bd6c36dcdf137607,

title = "Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses",

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.",

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

year = "2017",

month = jan,

day = "17",

doi = "10.1016/j.immuni.2016.12.011",

language = "English",

volume = "46",

pages = "120--132",

journal = "Immunity",

issn = "1074-7613",

number = "1",

}

Druzd, D, Matveeva, O, Ince, L, Harrison, U, He, W, Schmal, C, Herzel, H, Tsang, AH, Kawakami, N, Leliavski, A, Uhl, O, Yao, L, Sander, LE, Chen, CS, Kraus, K, de Juan, A, Hergenhan, SM, Ehlers, M, Koletzko, B, Haas, R, Solbach, W , Oster, H & Scheiermann, C 2017, 'Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses', Immunity, vol. 46, no. 1, pp. 120-132. https://doi.org/10.1016/j.immuni.2016.12.011

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 -

Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses

Abstract

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this