Beyond Neurotransmission: The Immunological Mechanism of ACh from The CAIP Perspective

School of Life Sciences, Sun Yat-sen University, Guangdong, China

^* Corresponding author: wangsy96@mail2.sysu.edu.cn

Abstract

Acetylcholine (ACh), traditionally recognized as a neurotransmitter involved in synaptic signaling, has emerged as a crucial player in the immune system, extending beyond its classical functions. Extensive scientific research has shed light on the intricate mechanisms underlying the cholinergic antiinflammatory pathway (CAIP), which plays a pivotal role in regulating immune responses and preserving homeostasis. Primarily mediated by the vagus nerve, this pathway involves the interaction between the nervous and immunological systems. ACh, acting as a key signaling molecule, exerts anti-inflammatory effects by modulating immune cell polarization (encompassing both morphological and functional changes), cytokine production, and signaling pathways. T cells and macrophages, equipped with the cholinergic system, prominently contribute to this immunomodulatory process. Nevertheless, the precise mechanisms governing the CAIP and the specific contribution of ACh in immunological responses remain subjects of ongoing research and debate. This concise review explores the intricate neuro-immune interactions, with a particular focus on the CAIP. Additionally, we delve into the cholinergic system within immune cells, examining the influence of lymphocyte-derived ACh on immunological functioning, thereby illuminating its regulatory role in immune responses and homeostasis maintenance, providing new insights into the development of innovative therapeutic strategies to combat inflammation-related diseases.