β-Adrenergic signaling blocks murine CD8+ T-cell metabolic reprogramming during activation: a mechanism for immunosuppression by adrenergic stress

Cancer Immunology, Immunotherapy : CII
Guanxi QiaoElizabeth A Repasky

Abstract

Primary and secondary lymphoid organs are heavily innervated by the autonomic nervous system. Norepinephrine, the primary neurotransmitter secreted by post-ganglionic sympathetic neurons, binds to and activates β-adrenergic receptors expressed on the surface of immune cells and regulates the functions of these cells. While it is known that both activated and memory CD8+ T-cells primarily express the β2-adrenergic receptor (β2-AR) and that signaling through this receptor can inhibit CD8+ T-cell effector function, the mechanism(s) underlying this suppression is not understood. Under normal activation conditions, T-cells increase glucose uptake and undergo metabolic reprogramming. In this study, we show that treatment of murine CD8+ T-cells with the pan β-AR agonist isoproterenol (ISO) was associated with a reduced expression of glucose transporter 1 following activation, as well as decreased glucose uptake and glycolysis compared to CD8+ T-cells activated in the absence of ISO. The effect of ISO was specifically dependent upon β2-AR, since it was not seen in adrb2-/- CD8+ T-cells and was blocked by the β-AR antagonist propranolol. In addition, we found that mitochondrial function in CD8+ T-cells was also impaired by β2-AR signali...Continue Reading

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Methods Mentioned

BETA
flow cytometry
by flow cytometry

Software Mentioned

ImageStream
FlowJo

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