The Role of α7nAChR-Mediated Cholinergic Anti-inflammatory Pathway in Immune Cells

Alpha 7 nicotinic acetylcholine receptor (α7nAChR) is widely distributed in the nervous and non-cholinergic immune systems. It is necessary for the cholinergic transmitter to participate in the regulation of inflammatory response and is the key element of cholinergic anti-inflammatory pathway (CAP). Because of the profound impact of CAP on the immune system, α7nAChR is considered as a potential therapeutic target for the treatment of inflammatory diseases. Available evidences confirmed that manipulation of CAP by activating α7nAChR with either endogenous acetylcholine (ACh) or cholinergic agonists can substantially alleviate inflammatory responses both in vivo and in vitro. However, the mechanism through which CAP curbs the excessive pro-inflammatory responses and maintains immune homeostasis is not fully understood. Obtained clues suggest that the crosstalk between CAP and classical inflammatory pathways is the key to elucidate the anti-inflammatory mechanism, and the impacts of CAP activation in α7nAChR-expressing immune cells are the foundation of the immunoregulatory property. In this article, we review and update the knowledge concerning the progresses of α7nAChR-based CAP, including α7nAChR properties, signal transductions, interactions with classic immune pathways, and immunoregulatory functions in different immune cells. Certain critical issues to be addressed are also highlighted. By providing a panoramic view of α7nAChR, the summarized evidences will pave the way for the development of novel anti-inflammatory reagents and strategy and inspire further researches.