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Adrenergic nerves govern circadian leukocyte recruitment to tissues

Kunisaki, Yuya
Lucas, Daniel
Chow, Andrew
Jang, Jung-Eun
Zhang, Dachuan
Hashimoto, Daigo
Merad, Miriam
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Published in Immunity. 2012, vol. 37, no. 2, p. 290-301
Abstract 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.
Keywords Adrenergic Fibers/immunology/metabolismAdrenergic Neurons/immunology/metabolismAnemia, Sickle Cell/immunologyAnimalsBone Marrow/metabolismBone Marrow Transplantation/immunologyCell Adhesion/immunologyCell Movement/immunologyChemokines/metabolismCircadian Rhythm/immunologyDisease Models, AnimalFlow CytometryGreen Fluorescent ProteinsHumansImmunohistochemistryIntercellular Adhesion Molecule-1/geneticsIsoproterenol/administration & dosageLeukocytes/immunologyMiceMice, Inbred C57BLMice, KnockoutReceptors, Adrenergic, beta/metabolismShock, Septic/immunologySympathetic Nervous System/cytology/immunology/metabolismTime Factors
PMID: 22863835
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Research group L'influence du rôle du cycle circadien sur l'immunité (995)
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SCHEIERMANN, Christoph et al. Adrenergic nerves govern circadian leukocyte recruitment to tissues. In: Immunity, 2012, vol. 37, n° 2, p. 290-301. doi: 10.1016/j.immuni.2012.05.021

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Deposited on : 2019-01-31

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