Published:April 28, 2021DOI:https://doi.org/10.1016/j.immuni.2021.03.025
Highlights
- •Activation of the sympathetic nervous system halts leukocyte locomotion in tissues
- •Noradrenaline induces adrenergic receptor signaling to reduce lymph node blood flow
- •Decreased tissue oxygenation induces calcium signaling to control leukocyte motility
- •Disruption of leukocyte motility contributes to impaired immune responses
Summary
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.
Graphical abstract
https://www.cell.com/immunity/fulltext/S1074-7613(21)00137-0#.YLW6t9Xr-H8.facebook
