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
IMMUNITY | CELL PRESS | Published : 2021
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 decrease..View full abstract
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Awarded by National Health and Medical Research Council of Australia
Awarded by Australian Research Council
We thank Tsuneyasu Kaisho for the XCR1venus mice; Dorian McGavern, Pamela Schwartzberg, and Tuoqi Wu for the GCaMP6s mice; Virginia Sanders for BALB/c-Adrb2 ~/~ mice; and Francis Carbone, Robin McAllen, John Furness, Roger Summers, Christopher Langmead, Daniel Poole, Michelle Halls, John Haynes, Connie Wong, Aeson Chang, Gavin Lambert, and Stephen Kent for help, advice, and discussions. This work was supported by the National Health and Medical Research Council of Australia (1082450 to S.N.M. and E.K.S., 1161734 to S.N.M., 1154457 to W.R.H., and 1147498 to E.K.S.) and the Australian Research Council (CE140100011 to W.R.H. and S.N.M.).