4.4 Review

Neuroimmune interactions and kidney disease

Journal

KIDNEY RESEARCH AND CLINICAL PRACTICE
Volume 38, Issue 3, Pages 282-294

Publisher

KOREAN SOC NEPHROLOGY
DOI: 10.23876/j.krcp.19.014

Keywords

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

Funding

  1. JSPS KAKENHI [19J11928, 18H06192, 18H02727]
  2. Grants-in-Aid for Scientific Research [19J11928, 18H02727, 18H06192] Funding Source: KAKEN

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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 beta 2 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.

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