11 April 2023

Some T cells in human blood can produce a substance that may help to regulate blood pressure and inflammation, new research from Sweden has found.

A team at Karolinska Institutet not only found that acetylcholine produced by T cells can regulate blood flow in humans, but also demonstrated a possible association between these immune cells in seriously ill patients and the risk of death.

The findings are published in the journal PNAS.

Although blood flow regulation by acetylcholine is long established in animal models, the sources of acetylcholine in human blood have remained unclear.

Choline acetyltransferase (ChAT) is an enzyme which makes acetylcholine. Previous research in mice has shown that ChAT-positive T cells can produce acetylcholine and affect endothelial cells in the blood vessels. However, it was not known if these types of T cells exist in humans.

The study’s joint-first author Dr Laura Tarnawski, from the Karolinska Institutet, said their study corroborates previous findings in different model systems, and may contribute to the development of treatments for cardiovascular disease and inflammatory diseases.

The findings are based on analyses of blood from healthy blood donors. The team also studied 33 patients with severe circulatory failure who had been admitted to intensive care hospital treatment. They found that higher relative blood levels of ChAT+ T cells were associated with reduced risk of death.

The other joint-first author, Dr Vladimir Shavva, said: “Our new study shows that acetylcholine in the blood can be secreted by immune cells, which can regulate inflammation in the blood vessels.”

The group now plans to map the presence of ChAT+ T cells in different patient groups and different organs, and how they affect metabolic and inflammatory processes.

Source:

Tarnawski L, Shavva VS, Kort EJ, Zhuge Z, Nilsson I, Gallina AL, Martínez-Enguita D, Heller Sahlgren B, Weiland M, Caravaca AS, Schmidt S, Chen P, Abbas K, Wang FH, Ahmed O, Eberhardson M, Färnert A, Weitzberg E, Gustafsson M, Kehr J, Malin SG, Hult H, Carlström M, Jovinge S, Olofsson PS.  (2023) “Cholinergic regulation of vascular endothelial function by human ChAT+ T cells.” PNAS, doi: 10.1073/pnas.2212476120.

Link: https://www.pnas.org/doi/10.1073/pnas.2212476120

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