Targeting Neural Reflex Circuits in Immunity to Treat Kidney Disease

Overview

Journal Nat Rev Nephrol

Specialty Nephrology

Date 2017 Oct 4

PMID 28970585

Citations 38

Authors

Mark D Okusa

Diane L Rosin

Kevin J Tracey

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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References

Kopp U, Cicha M, Smith L, Hokfelt T . Nitric oxide modulates renal sensory nerve fibers by mechanisms related to substance P receptor activation. Am J Physiol Regul Integr Comp Physiol. 2001; 281(1):R279-90. DOI: 10.1152/ajpregu.2001.281.1.R279. View

Joyner M, Charkoudian N, Wallin B . Sympathetic nervous system and blood pressure in humans: individualized patterns of regulation and their implications. Hypertension. 2010; 56(1):10-6. PMC: 2891078. DOI: 10.1161/HYPERTENSIONAHA.109.140186. View

Madhur M, Lob H, McCann L, Iwakura Y, Blinder Y, Guzik T . Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2009; 55(2):500-7. PMC: 2819301. DOI: 10.1161/HYPERTENSIONAHA.109.145094. View

Hering D, Mahfoud F, Walton A, Krum H, Lambert G, Lambert E . Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012; 23(7):1250-7. PMC: 3380649. DOI: 10.1681/ASN.2011111062. View

Abe C, Inoue T, Inglis M, Viar K, Huang L, Ye H . C1 neurons mediate a stress-induced anti-inflammatory reflex in mice. Nat Neurosci. 2017; 20(5):700-707. PMC: 5404944. DOI: 10.1038/nn.4526. View

Brouns I, Adriaensen D, Burnstock G, Timmermans J . Intraepithelial vagal sensory nerve terminals in rat pulmonary neuroepithelial bodies express P2X(3) receptors. Am J Respir Cell Mol Biol. 2000; 23(1):52-61. DOI: 10.1165/ajrcmb.23.1.3936. View

Kim J, Padanilam B . Renal denervation prevents long-term sequelae of ischemic renal injury. Kidney Int. 2014; 87(2):350-8. PMC: 4312521. DOI: 10.1038/ki.2014.300. View

Chatterjee P, Yeboah M, Dowling O, Xue X, Powell S, Al-Abed Y . Nicotinic acetylcholine receptor agonists attenuate septic acute kidney injury in mice by suppressing inflammation and proteasome activity. PLoS One. 2012; 7(5):e35361. PMC: 3346807. DOI: 10.1371/journal.pone.0035361. View

Williams E, Chang R, Strochlic D, Umans B, Lowell B, Liberles S . Sensory Neurons that Detect Stretch and Nutrients in the Digestive System. Cell. 2016; 166(1):209-21. PMC: 4930427. DOI: 10.1016/j.cell.2016.05.011. View

10.

Hotchkiss R, Monneret G, Payen D . Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013; 13(12):862-74. PMC: 4077177. DOI: 10.1038/nri3552. View

11.

Rosas-Ballina M, Olofsson P, Ochani M, Valdes-Ferrer S, Levine Y, Reardon C . Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011; 334(6052):98-101. PMC: 4548937. DOI: 10.1126/science.1209985. View

12.

Rosas-Ballina M, Ochani M, Parrish W, Ochani K, Harris Y, Huston J . Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc Natl Acad Sci U S A. 2008; 105(31):11008-13. PMC: 2504833. DOI: 10.1073/pnas.0803237105. View

13.

Mascarucci P, Perego C, Terrazzino S, De Simoni M . Glutamate release in the nucleus tractus solitarius induced by peripheral lipopolysaccharide and interleukin-1 beta. Neuroscience. 1998; 86(4):1285-90. DOI: 10.1016/s0306-4522(98)00105-5. View

14.

De Ferrari G, Crijns H, Borggrefe M, Milasinovic G, Smid J, Zabel M . Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. Eur Heart J. 2010; 32(7):847-55. DOI: 10.1093/eurheartj/ehq391. View

15.

Jansen A, Nguyen X, Karpitskiy V, Mettenleiter T, Loewy A . Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response. Science. 1995; 270(5236):644-6. DOI: 10.1126/science.270.5236.644. View

16.

Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G . Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension. 1988; 11(1):3-20. DOI: 10.1161/01.hyp.11.1.3. View

17.

Andersson U, Tracey K . Neural reflexes in inflammation and immunity. J Exp Med. 2012; 209(6):1057-68. PMC: 3371736. DOI: 10.1084/jem.20120571. View

18.

Bautista L, Vera L, Arenas I, Gamarra G . Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. J Hum Hypertens. 2004; 19(2):149-54. DOI: 10.1038/sj.jhh.1001785. View

19.

Hermes S, Colbert J, Aicher S . Differential content of vesicular glutamate transporters in subsets of vagal afferents projecting to the nucleus tractus solitarii in the rat. J Comp Neurol. 2013; 522(3):642-53. PMC: 3877231. DOI: 10.1002/cne.23438. View

20.

Herrera J, Ferrebuz A, MacGregor E, Rodriguez-Iturbe B . Mycophenolate mofetil treatment improves hypertension in patients with psoriasis and rheumatoid arthritis. J Am Soc Nephrol. 2006; 17(12 Suppl 3):S218-25. DOI: 10.1681/ASN.2006080918. View