Adrenergic Nerves Affect Immune System Circadian Rhythms

The adrenergic nervous system controls when white blood cells circulate through the body, researchers in Japan have discovered. The effect boosts the immune response by retaining B and T cells in lymph nodes at the time of day when they are most likely to encounter foreign antigens.

As they circulate through the body, T and B cells pass through lymph nodes, where specialized cells may present them with antigen molecules captured from bacteria or other pathogens. The T and B cells then reenter the bloodstream in search of these pathogens so that they can kill them and fight off infection.

Previous studies have suggested that number of T and B cells present in the bloodstream varies over the course of the day.

The adrenergic nervous system is a group of organs and nerves in which adrenaline and/or norepinephrine act as neurotransmitters. It is considered one of the main neurohormonal systems regulating cardiovascular function.

Noradrenaline Regulated

Kazuhiro Suzuki and colleagues from the WPI Immunology Frontier Research Center at Osaka University found that, in mice, the number of T and B cells in the blood peaked during the day and decreased during the night, when they accumulated in lymph nodes instead. This daily, or circadian, cycle of immune cell trafficking was regulated by the neurotransmitter noradrenaline, released from adrenergic nerves innervating the lymph nodes.

The nerves secreted more noradrenaline at night, activating β2-adrenergic receptor molecules on the surface of T and B cells that impede the cells’ exit from lymph nodes.

Mice had a stronger immune response if they were injected with antigens at night, when more of their T and B cells were exposed to antigen-presenting cells in lymph nodes. This is logical, Suzuki and colleagues say, because mice are nocturnal animals, and so are more likely to encounter pathogens when they are active during the night.

Accordingly, the daily cycle may be flipped in humans, whose T and B cells appear to accumulate in lymph nodes during the day, when adrenergic nerves are thought to be more active.

The study uncovers adrenergic control of lymphocyte trafficking’s physiological role in adaptive immunity and establishes a novel mechanism that generates diurnal rhythmicity in the immune system.

Kazuhiro Suzuki, Yuki Hayano, Akiko Nakai, Fumika Furuta, Masaki Noda
Adrenergic control of the adaptive immune response by diurnal lymphocyte recirculation through lymph nodes
Journal of Experimental Medicine Oct 2016, jem.20160723; DOI: 10.1084/jem.20160723

Image: mouse lymph node. Credit: Kazuhiro Suzuki