TY - JOUR
T1 - Adrenergic nerves govern circadian leukocyte recruitment to tissues
AU - Scheiermann, Christoph
AU - Kunisaki, Yuya
AU - Lucas, Daniel
AU - Chow, Andrew
AU - Jang, Jung Eun
AU - Zhang, Dachuan
AU - Hashimoto, Daigo
AU - Merad, Miriam
AU - Frenette, Paul S.
N1 - Funding Information:
We thank R. Sellers for histopathological examinations, L. Tesfa for cell-sorting experiments, and C. Prophete, M. Huggins, and N. Dholakia for technical assistance. This work was supported by the National Institutes of Health (NIH) (R01 grants HL097700; HL069438; DK056638) to P.S.F. We are grateful for fellowship support from the German Academic Exchange Service (DAAD) to C.S., the Japan Society for the Promotion of Science to Y.K., the Fundación Ramón Areces to D.L., a Ruth L. Kirschstein National Research Service Award from the National Heart, Lung, and Blood Institute (NHLBI) (F30HL099028) to A.C., and a Founders Affiliate Predoctoral Fellowship from the American Heart Association to J.-E.J.
PY - 2012/8/24
Y1 - 2012/8/24
N2 - The multistep sequence leading to leukocyte migration is thought to be locally regulated at the inflammatory site. Here, we show that broad systemic programs involving long-range signals from the sympathetic nervous system (SNS) delivered by adrenergic nerves regulate rhythmic recruitment of leukocytes in tissues. Constitutive leukocyte adhesion and migration in murine bone marrow (BM) and skeletal-muscle microvasculature fluctuated with circadian peak values at night. Migratory oscillations, altered by experimental jet lag, were implemented by perivascular SNS fibers acting on β-adrenoreceptors expressed on nonhematopoietic cells and leading to tissue-specific, differential circadian oscillations in the expression of endothelial cell adhesion molecules and chemokines. We showed that these rhythms have physiological consequences through alteration of hematopoietic cell recruitment and overall survival in models of septic shock, sickle cell vaso-occlusion, and BM transplantation. These data provide unique insights in the leukocyte adhesion cascade and the potential for time-based therapeutics for transplantation and inflammatory diseases.
AB - The multistep sequence leading to leukocyte migration is thought to be locally regulated at the inflammatory site. Here, we show that broad systemic programs involving long-range signals from the sympathetic nervous system (SNS) delivered by adrenergic nerves regulate rhythmic recruitment of leukocytes in tissues. Constitutive leukocyte adhesion and migration in murine bone marrow (BM) and skeletal-muscle microvasculature fluctuated with circadian peak values at night. Migratory oscillations, altered by experimental jet lag, were implemented by perivascular SNS fibers acting on β-adrenoreceptors expressed on nonhematopoietic cells and leading to tissue-specific, differential circadian oscillations in the expression of endothelial cell adhesion molecules and chemokines. We showed that these rhythms have physiological consequences through alteration of hematopoietic cell recruitment and overall survival in models of septic shock, sickle cell vaso-occlusion, and BM transplantation. These data provide unique insights in the leukocyte adhesion cascade and the potential for time-based therapeutics for transplantation and inflammatory diseases.
UR - http://www.scopus.com/inward/record.url?scp=84865367519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865367519&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2012.05.021
DO - 10.1016/j.immuni.2012.05.021
M3 - Article
C2 - 22863835
AN - SCOPUS:84865367519
SN - 1074-7613
VL - 37
SP - 290
EP - 301
JO - Immunity
JF - Immunity
IS - 2
ER -