Signals of vagal circuits engaging with AKT1 in α7 nAChR(+)CD11b(+) cells lessen E. coli and LPS-induced acute inflammatory injury

Cell Discovery
Caiqi ZhaoXiao Su

Abstract

Vagal circuits-α7 nAChR (α7 nicotinic acetylcholine receptor, coded by Chrna7) signaling utilizes spleen as a hub to dampen systemic inflammatory responses. Vagal innervations also extend to the distal airways and alveoli. Vagotomy and deficiency of α7 nAChR deteriorate E. coli and lipopolysaccharide (LPS)-induced acute lung inflammatory responses; however, the underlying mechanisms remain elusive. Here, we hypothesized that vagal circuits would limit splenic release and lung recruitment of α7 nAChR(+)CD11b(+) cells (CD11b is coded by Itgam, a surface marker of monocytes and neutrophils) via phosphorylation of AKT1 and that this process would define the severity of lung injury. Using both E. coli and LPS-induced lung injury mouse models, we found that vagotomy augmented splenic egress and lung recruitment of α7 nAChR(+)CD11b(+) cells, and consequently worsened lung inflammatory responses. Rescue of vagotomy with an α7 nAChR agonist preserved α7 nAChR(+)CD11b(+) cells in the spleen, suppressed recruitment of these cells to the lung and attenuated lung inflammatory responses. Vagal signals via α7 nAChR promoted serine473 phosphorylation of AKT1 in α7 nAChR(+)CD11b(+) cells and stabilized these cells in the spleen. Deletion of Akt...Continue Reading

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Citations

Nov 12, 2019·Journal of Internal Medicine·M A CoxT W Mak
Jul 18, 2018·QJM : Monthly Journal of the Association of Physicians·Y HuangX Su
Dec 19, 2018·Frontiers in Pharmacology·Mitsuhiro Yamada, Masakazu Ichinose
Jul 18, 2018·QJM : Monthly Journal of the Association of Physicians·Y HuangX Su

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Methods Mentioned

BETA
flow cytometry
ELISA
protein assay

Software Mentioned

GraphPad Prism
PathScan
Flowjo

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AKT Pathway

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