Acetylcholine stored in dendritic cells plays a role in the differentiation of naïve CD4+ T cells into a Th1 phenotype

Abstract

AbstractObjectiveImmune cells, particularly dendritic cells (DC), express choline acetyltransferase, an enzyme essential for the production of acetylcholine (ACh); thus, DC appear to store ACh. However, the immunological role of intracytoplasmic ACh within DC is largely unknown.MethodsTo examine the role of ACh during adaptive responses, naïve CD4+ T cells were stimulated with anti‐CD3 and anti‐CD28 antibodies in the presence or absence of ACh. Next, monocyte‐derived DC (Mo‐DC) were stained with an anti‐ACh antibody to investigate the intracytoplasmic storage of ACh.ResultsThe results showed that Mo‐DC stored ACh in the intracytoplasmic space. Stimulation with lipopolysaccharide (a Th1‐inducing agent) increased the levels of ACh in Mo‐DC; however, levels decreased under conditions that mimicked the interaction between DC and naïve CD4+ T cells. Interferon‐γ secretion increased preferentially in the presence of ACh, suggesting that naïve CD4+ T cells differentiate into T helper (Th)1 cells in the presence of ACh.ConclusionsThese observations suggest that Mo‐DC increase ACh storage in the presence of a Th1 adjuvant and release it during the interaction between DC and naïve CD4+ T cells, thereby driving their differentiation into Th1 cells. Thus, DC might utilize ACh to regulate the Th1 population in response to certain antigens.