Journal Article

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

Qiao, Guanxi, Winder, Nicolette M, Repasky, Elizabeth A, Hylander, Bonnie L, Bucsek, Mark J, Olejniczak, Scott H, Chen, Minhui, Giridharan, Thejaswini

2019

Overview

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 signaling. This study demonstrates that one mechanism by which β2-AR signaling can inhibit CD8+ T-cell activation is by suppressing the required metabolic reprogramming events which accompany activation of these immune cells and thus reveals a new mechanism by which adrenergic stress can suppress the effector activity of immune cells.

• Publisher: Springer Nature B.V
• Subject: Adrenergic receptors / Autonomic nervous system / CD8 antigen / Cell activation / Effector cells / Glucose / Glucose transporter / Glycolysis / Immunological memory / Immunosuppression / Isoproterenol / Lymphocytes T / Memory cells / Metabolic rate / Metabolism / Mitochondria / Norepinephrine / Propranolol / Sympathetic nerves / T cell receptors