Innervation of immune cells: Evidence for neuroimmunomodulation in the liver

Neuhuber, Winfried; Tiegs, Gisa

doi:10.1002/ar.a.20093

Cited by 36 publications

(21 citation statements)

References 51 publications

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“…This study identifies extracellular ATP as a hepatic mitogen with implications about the regulation of liver growth and repair. Sympathetic nerves using NA and ATP as cotransmitters alleviate immunemediated experimental hepatitis in the mouse; it is speculated that nerve-immune cell interactions may offer novel therapeutic strategies in immune and inflammatory liver diseases (Neuhuber and Tiegs, 2004).…”

Section: Gastroenterologymentioning

confidence: 99%

Pathophysiology and Therapeutic Potential of Purinergic Signaling

2006

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Section: Gastroenterologymentioning

confidence: 99%

Pathophysiology and Therapeutic Potential of Purinergic Signaling

2006

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“…2,3 We recently reported that liver inflammation is also modulated by the autonomic nervous system. 4,5 Sympathetic efferent as well as primary sensory neurons are key players in the regulation of peripheral inflammation and immune responses. 1 Primary sensory neurons innervating inner organs are composed mainly of the peptidergic subpopulation of B-type primary afferents giving rise to unmyelinated C and thin myelinated A␦ fibers.…”

mentioning

confidence: 99%

“…15 The bidirectional communication between the nervous and immune systems results from the expression of specific receptors for cytokines and other immune mediators on neurons, as well as for neurotransmitters and neuropeptides on immune cells. 5,14 Although the kidney is frequently affected by immune-mediated pathologies such as various forms of glomerulonephritis (GN) or lupus erythematodes, to our knowledge, neuroimmune interactions have never been studied in this organ. Renal innervation consists of sympathetic and primary sensory nerve fibers.…”

mentioning

confidence: 99%

Autonomic Renal Denervation Ameliorates Experimental Glomerulonephritis

Veelken

Vogel

Hilgers

et al. 2008

Journal of the American Society of Nephrology

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100

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Increasing evidence indicates that inflammation of visceral organs is significantly affected by the autonomic nervous system. Such neuroimmune interactions have not been studied in the kidney. Here, we show that the rat kidney is innervated by both tyrosine hydroxylase-positive sympathetic efferent nerve fibers and calcitonin gene-related peptide-positive primary afferent nerve fibers, both of which are found in proximity to macrophages and dendritic cells. Complete surgical bilateral renal denervation was performed 2 d before glomerulonephritis was induced by injecting the monoclonal anti-Thy-1.1 antibody OX-7. Denervation significantly reduced albuminuria, mesangiolysis, formation of microaneurysms, deposition of glomerular collagen IV, and expression of TGF-␤ compared with sham-operated controls. Accordingly, inflammation, identified by accumulation of interstitial macrophages and renal expression of TNF-␣, and mesangial cell proliferation were significantly reduced. These findings indicate that autonomic renal denervation ameliorates and, by inference, innervation exacerbates acute inflammation in the kidney; therefore, neurotransmitters or neuropeptides and their receptors might represent novel targets for the treatment of acute glomerulonephritis.

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“…An influence of sympathetic nerves in immunemediated experimental hepatitis has been demonstrated [188], and ATP released as a cotransmitter might be involved. P2X7 receptors regulate NKT cells in autoimmune hepatitis [144].…”

Section: Hepatitismentioning

confidence: 99%

Purinergic signalling in the liver in health and disease

Burnstock

Vaughn

Robson

2013

Purinergic Signalling

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Purinergic signalling is involved in both the physiology and pathophysiology of the liver. Hepatocytes, Kupffer cells, vascular endothelial cells and smooth muscle cells, stellate cells and cholangiocytes all express purinoceptor subtypes activated by adenosine, adenosine 5′-triphosphate, adenosine diphosphate, uridine 5′-triphosphate or UDP. Purinoceptors mediate bile secretion, glycogen and lipid metabolism and indirectly release of insulin. Mechanical stress results in release of ATP from hepatocytes and Kupffer cells and ATP is also released as a cotransmitter with noradrenaline from sympathetic nerves supplying the liver. Ectonucleotidases play important roles in the signalling process. Changes in purinergic signalling occur in vascular injury, inflammation, insulin resistance, hepatic fibrosis, cirrhosis, diabetes, hepatitis, liver regeneration following injury or transplantation and cancer. Purinergic therapeutic strategies for the treatment of these pathologies are being explored.

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Innervation of immune cells: Evidence for neuroimmunomodulation in the liver

Cited by 36 publications

References 51 publications

Pathophysiology and Therapeutic Potential of Purinergic Signaling

Pathophysiology and Therapeutic Potential of Purinergic Signaling

Autonomic Renal Denervation Ameliorates Experimental Glomerulonephritis

Purinergic signalling in the liver in health and disease

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