T Cells Found to Produce Acetylcholine to Regulate Inflammation

Scientists at Karolinska Institutet in Sweden have learned that certain T cells in human blood can produce acetylcholine, which may help regulate blood pressure and inflammation. The research, which was published in the Proceedings of the National Academy of Sciences (PNAS), found that higher relative blood levels of ChAT+ T cells were associated with reduced risk of death in severely ill patients with excessive inflammation.

The researchers found that human T cells can release acetylcholine, corroborating previous findings in different model systems. This discovery may contribute to developing treatments for cardiovascular and inflammatory diseases. The team also found that acetylcholine in the blood can be secreted by immune cells, which can regulate inflammation in the blood vessels.

The team analyzed blood from healthy blood donors and studied 33 patients with severe circulatory failure who had been admitted for intensive care. The study's findings are of clinical interest and could contribute to new diagnostic and therapeutic opportunities for seriously ill patients with excessive inflammation.

In functional experiments, T cell-derived acetylcholine increased endothelial nitric oxide synthase activity, promoted vasorelaxation, reduced vascular endothelial activation, and promoted barrier integrity by a cholinergic mechanism. These findings on ChAT+ human T cells provide a mechanism for cholinergic immune regulation of vascular endothelial function in human inflammation.

The researchers identified that ChAT mRNA expression was induced by T cell activation involving the PI3K signaling cascade. They also determined that GATA3 up-regulated ChAT mRNA expression levels in human T cells.

The discovery of T cells in human blood that can produce acetylcholine is groundbreaking and provides new insight into regulating blood pressure and inflammation. The findings may significantly impact the development of new diagnostic and therapeutic opportunities for patients with cardiovascular and inflammatory diseases. The researchers plan to continue their work to map the presence of ChAT+ T cells in different patient groups and organs and to investigate how they affect metabolic and inflammatory processes.