Celiac vagus nerve mediates expression of the acetylcholine receptor a7nAChR on monocytes in the spleen

The spleen is required for the vagal cholinergic anti-inflammatory activity to maintain systemic immune homeostasis, but the underlying mechanism of this function is not fully understood yet. We hypothesized that vagus nerve mediates alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) expression in monocytes, an essential regulator of cholinergic anti-inflammatory activity, and the spleen is essential site for this process. To verify this hypothesis, mice were subjected to splenectomy or celiac vagotomy. The level of alpha 7nAChR expression in circulating monocytes was analyzed by real-time PCR. Impact of alpha 7nAChR agonist PNU282987 on LPS-evoked release of TNF-alpha and IL-1 beta from circulating monocytes was assessed by ELISA. The effect of norepinephrine (NE), acetylcholine (ACh) and neuregulin-1 (NRG-1) on alpha 7nAChR expression was detected by real-time PCR. We found that splenectomy or celiac vagotomy abrogated alpha 7nAChR expression in circulating monocytes. LPS-induced release of TNF-alpha and IL-1 beta from these monocytes was not alleviated significantly by PNU282987 as compared with that of sham mice. NE and ACh addition fails to stimulate alpha 7nAChR expression, but, NRG-1 treatment can significantly induce alpha 7nAChR expression in these monocytes compared with untreated cells in vitro. Overall, our results reveal that celiac vagus nerve mediates alpha 7nAChR expression in monocytes, and the spleen is indispensable site for this process. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

The spleen plays a crucial role in maintaining the vagal cholinergic anti-inflammatory activity, and this function involves the regulation of alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) expression in monocytes by the vagus nerve. The spleen is an indispensable site for this process.