Adrenergic nerves govern circadian leukocyte recruitment to tissues

Christoph Scheiermann, Yuya Kunisaki, Daniel Lucas, Andrew Chow, Jung Eun Jang, Dachuan Zhang, Daigo Hashimoto, Miriam Merad, Paul S. Frenette

Research output: Contribution to journalArticlepeer-review

389 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)290-301
Number of pages12
Issue number2
Publication statusPublished - Aug 24 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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