The Neuroimmune Axis in the Kidney

Touyz, Rhian M.

doi:10.1161/circresaha.115.307176

Cited by 5 publications

(6 citation statements)

References 23 publications

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“…Although increased sympathetic nerve activity seems to have both activating and suppressive effects on the immune system (dependent in part on the effects on immune cells in different locations), direct evidence indicates that increased sympathetic outflow and the resulting increase in noradrenaline levels activates T cells, promotes renal inflammation and contributes to hypertension 140 . These neural-immune mechanisms are mediated at least in part by T cells in the kidney, which have roles in immune-mediated damage 141–143 and salt-sensitive hypertension 144,145 .…”

Section: Neuroimmunomodulatory Pathwaysmentioning

confidence: 99%

“…Renal sympathetic nerves drive T cell infiltration, kidney damage and hypertension 140,146 . In turn, hypertension causes accumulation of oxidized products (γ-ketoaldehydes) in dendritic cells, which promotes dendritic cell cytokine production and activates T cells 146 .…”

Section: Neuroimmunomodulatory Pathwaysmentioning

confidence: 99%

“…These new concepts are provocative but the mechanisms need to be more clearly defined to resolve potential inconsistences 140 . A role for neural-immune mechanisms in the kidney also needs to be confirmed in human hypertension.…”

Section: Neuroimmunomodulatory Pathwaysmentioning

confidence: 99%

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Targeting neural reflex circuits in immunity to treat kidney disease

2017

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Neural pathways regulate immunity and inflammation via the inflammatory reflex and specific molecular targets can be modulated by stimulating neurons. Neuroimmunomodulation by nonpharmacological methods is emerging as a novel therapeutic strategy for inflammatory diseases, including kidney diseases and hypertension. Electrical stimulation of vagus neurons or treatment with pulsed ultrasound activates the cholinergic anti-inflammatory pathway (CAP) and protects mice from acute kidney injury (AKI). Direct innervation of the kidney, by afferent and efferent neurons, might have a role in modulating and responding to inflammation in various diseases, either locally or by providing feedback to regions of the central nervous system that are important in the inflammatory reflex pathway. Increased sympathetic drive to the kidney has a role in the pathogenesis of hypertension, and selective modulation of neuroimmune interactions in the kidney could potentially be more effective for lowering blood pressure and treating inflammatory kidney diseases than renal denervation. Use of optogenetic tools for selective stimulation of specific neurons has enabled the identification of neural circuits in the brain that modulate kidney function via activation of the CAP. In this Review we discuss evidence for a role of neural circuits in the control of renal inflammation as well as the therapeutic potential of targeting these circuits in the settings of AKI, kidney fibrosis and hypertension.

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Section: Neuroimmunomodulatory Pathwaysmentioning

confidence: 99%

Section: Neuroimmunomodulatory Pathwaysmentioning

confidence: 99%

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Targeting neural reflex circuits in immunity to treat kidney disease

2017

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“…Moreover, high abundance of the A 3 receptor has been demonstrated in immune cells, including dendritic cells and lymphocytes, and a role for the A 3 receptor has been suggested in diseases involving inflammation (eg, ischemia reperfusion injury, pain, autoimmune diseases) . In addition, accumulating evidence demonstrates that the immune system is directly involved in the pathogenesis and development of both hypertension and CKD …”

Section: Introductionmentioning

confidence: 99%

“…22,23 In addition, accumulating evidence demonstrates that the immune system is directly involved in the pathogenesis and development of both hypertension and CKD. [24][25][26][27] In the current study using UNX-HS, which induces hypertension and CKD, we investigated the role of the adenosine A 3 receptor. We hypothesized that abrogation of adenosine A 3 receptor signaling could attenuate cardiovascular abnormalities and renal injuries in this model of hypertension through modulation of oxidative stress and inflammation.…”

mentioning

confidence: 99%

Genetic Abrogation of Adenosine A ₃ Receptor Prevents Uninephrectomy and High Salt–Induced Hypertension

Yang

Zollbrecht

Winerdal

et al. 2016

JAHA

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BackgroundEarly‐life reduction in nephron number (uninephrectomy [UNX]) and chronic high salt (HS) intake increase the risk of hypertension and chronic kidney disease. Adenosine signaling via its different receptors has been implicated in modulating renal, cardiovascular, and metabolic functions as well as inflammatory processes; however, the specific role of the A3 receptor in cardiovascular diseases is not clear. In this study, gene‐modified mice were used to investigate the hypothesis that lack of A3 signaling prevents the development of hypertension and attenuates renal and cardiovascular injuries following UNX in combination with HS (UNX‐HS) in mice.Methods and ResultsWild‐type (A3 +/+) mice subjected to UNX‐HS developed hypertension compared with controls (mean arterial pressure 106±3 versus 82±3 mm Hg; P<0.05) and displayed an impaired metabolic phenotype (eg, increased adiposity, reduced glucose tolerance, hyperinsulinemia). These changes were associated with both cardiac hypertrophy and fibrosis together with renal injuries and proteinuria. All of these pathological hallmarks were significantly attenuated in the A3 −/− mice. Mechanistically, absence of A3 receptors protected from UNX‐HS–associated increase in renal NADPH oxidase activity and Nox2 expression. In addition, circulating cytokines including interleukins 1β, 6, 12, and 10 were increased in A3 +/+ following UNX‐HS, but these cytokines were already elevated in naïve A3 −/− mice and did not change following UNX‐HS.ConclusionsReduction in nephron number combined with chronic HS intake is associated with oxidative stress, chronic inflammation, and development of hypertension in mice. Absence of adenosine A3 receptor signaling was strongly protective in this novel mouse model of renal and cardiovascular disease.

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