Adrenergic regulation of the vasculature impairs leukocyte interstitial migration and suppresses immune responses

Sapna Devi, Yannick O. Alexandre, Joon Keit Loi, Ryan Gillis, Nazanin Ghazanfari, Sarah J. Creed, Lauren E. Holz, David Shackleford, Laura K. Mackay, William R. Heath, Erica K. Sloan, Scott N. Mueller

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

The sympathetic nervous system (SNS) controls various physiological functions via the neurotransmitter noradrenaline. Activation of the SNS in response to psychological or physical stress is frequently associated with weakened immunity. Here, we investigated how adrenoceptor signaling influences leukocyte behavior. Intravital two-photon imaging after injection of noradrenaline revealed transient inhibition of CD8+ and CD4+ T cell locomotion in tissues. Expression of β-adrenergic receptor in hematopoietic cells was not required for NA-mediated inhibition of motility. Rather, chemogenetic activation of the SNS or treatment with adrenergic receptor agonists induced vasoconstriction and decreased local blood flow, resulting in abrupt hypoxia that triggered rapid calcium signaling in leukocytes and halted cell motility. Oxygen supplementation reversed these effects. Treatment with adrenergic receptor agonists impaired T cell responses induced in response to viral and parasitic infections, as well as anti-tumor responses. Thus, stimulation of the SNS impairs leukocyte mobility, providing a mechanistic understanding of the link between adrenergic receptors and compromised immunity.

Original languageEnglish
Pages (from-to)1219-1230.e7
Number of pages19
JournalImmunity
Volume54
Issue number6
DOIs
Publication statusPublished - 8 Jun 2021

Keywords

  • adrenergic receptor
  • cell motility
  • immune response
  • infection
  • intravital imaging
  • lymph nodes
  • neuro-immune interactions
  • noradrenaline
  • sympathetic nervous system
  • T lymphocytes

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