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

Devi, S; Alexandre, YO; Loi, JK; Gillis, R; Ghazanfari, N; Creed, SJ; Holz, LE; Shackleford, D; Mackay, LK; Heath, WR; Sloan, EK; Mueller, SN

Author(s): Devi, S; Alexandre, YO; Loi, JK; Gillis, R; Ghazanfari, N; Creed, SJ; Holz, LE; Shackleford, D; Mackay, LK; Heath, WR; Sloan, EK; Mueller, SN;
Details: Publication Year 2021-06,Volume 54,Issue #6,Page 1219-1230.e7
Journal Title: Immunity
Publication Type: Research article
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 beta-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.
Keywords: Adrenergic Agents/*immunology; Animals; Calcium Signaling/immunology; Cell Line, Tumor; Cell Movement/*immunology; Immunity/*immunology; Leukocytes/*immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Receptors, Adrenergic/immunology; Signal Transduction/immunology; Sympathetic Nervous System/*immunology; T-Lymphocytes/immunology; T lymphocytes; adrenergic receptor; cell motility; immune response; infection; intravital imaging; lymph nodes; neuro-immune interactions; noradrenaline; sympathetic nervous system
Department(s): Surgical Oncology
PubMed ID: 33915109
Publisher's Version: https://doi.org/10.1016/j.immuni.2021.03.025
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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