Kidney Res Clin Pract.  2019 Sep;38(3):282-294. 10.23876/j.krcp.19.014.

Neuroimmune interactions and kidney disease

Affiliations
  • 1Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
  • 2Division of CKD Pathophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. tsinoue-tky@umin.ac.jp

Abstract

The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a well-studied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic anti-inflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.

Keyword

Autonomic nervous system; Cholinergic neurons; Imaging; three-dimensional; Optogenetics; Sympathetic nervous system; Vagus nerve stimulation

MeSH Terms

Acetylcholine
Arteries
Autonomic Nervous System
Cholinergic Neurons
Homeostasis
Humans
Immune System
Inflammation
Kidney Diseases*
Kidney*
Macrophages
Nervous System
Neurotransmitter Agents
Norepinephrine
Optogenetics
Physiology
Receptors, Adrenergic
Receptors, Nicotinic
Reperfusion Injury
Spleen
Sympathectomy
Sympathetic Nervous System
T-Lymphocytes
Ultrasonography
Vagus Nerve
Vagus Nerve Stimulation
Acetylcholine
Neurotransmitter Agents
Norepinephrine
Receptors, Adrenergic
Receptors, Nicotinic
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