title: Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes.
abstract: The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Chikara
authors.initials: C
authors.lastname: Abe
authors.forename: Sun-Sang J
authors.initials: SS
authors.lastname: Sung
authors.forename: Stefan
authors.initials: S
authors.lastname: Moscalu
authors.forename: Jakub
authors.initials: J
authors.lastname: Jankowski
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Diane L
authors.initials: DL
authors.lastname: Rosin
authors.forename: Patrice G
authors.initials: PG
authors.lastname: Guyenet
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D055536:Vagus Nerve Stimulation; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000276:immunology*
chemical_list: D064569:alpha7 Nicotinic Acetylcholine Receptor