The Interactions Between Acetylcholine and T-Cells and Their Role in the Immune System: A Scoping Review

Acetylcholine (ACh) exhibits immunomodulatory functions beyond its conventional role as a neurotransmitter. T-cells possess the highest expression of cholinergic machinery, suggesting that the cholinergic system exists and may be important within the immune structure and function. The aim of this review was to examine the literature on ACh and its role and function in T-cells as a foundation for understanding the immunomodulatory effects on T-cells. A three-stage search strategy was conducted across three major databases. Non-English publications and articles published before 1990 were excluded. Screening and data extraction were performed independently by two reviewers. Sixty-six articles met the inclusion criteria. Over half (53%) were laboratory-based studies. Fifty-five studies investigated the physiological functions of cholinergic T-cells, and 30 studies explored systemic effects of cholinergic T-cell activity. Landmark studies from the 1990s revealed far-reaching implications of nonneuronal ACh in immune regulation and confirmed the critical role of ACh in T-cell function. However, the key mechanistic pathways remained underexplored warranting further investigation. Based on these studies we propose an underlying mechanism that could harness the full potential of cholinergic immune signalling, and unravel the immunomodulatory pathway.