Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase
Peder S Olofsson1,2, Benjamin E Steinberg2,3, Roozbeh Sobbi4
1Center for Bioelectronic Medicine, Department of Medicine, Center for Molecular Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Insights
Immune cells, specifically CD4 T cells expressing choline acetyltransferase (ChAT), play a role in blood pressure regulation. These cells help lower blood pressure by promoting nitric oxide release, suggesting new therapeutic targets.
Area of Science:
- Immunology
- Cardiovascular Physiology
- Neuroendocrinology
Background:
- Blood pressure is regulated by neuro-endocrine circuits.
- The role of immune cells in blood pressure homeostasis is largely unknown.
- CD4+ T lymphocytes expressing choline acetyltransferase (ChAT) were previously shown to relay neural signals.
Purpose of the Study:
- To determine if immune cells contribute to blood pressure homeostasis.
- To characterize a distinct T-cell population expressing ChAT (CD4 TChAT).
- To investigate the therapeutic potential of CD4 TChAT cells in blood pressure regulation.
Main Methods:
- Gene expression analysis to define CD4 TChAT cells.
- Studying blood pressure in mice lacking ChAT in CD4+ cells.
- Infusing Jurkat T cells overexpressing ChAT (JTChAT) into mice.
- Co-incubation of JTChAT and endothelial cells to measure nitric oxide release.
Main Results:
- Mice lacking ChAT in CD4+ cells exhibited elevated arterial blood pressure.
- Infusion of JTChAT cells decreased blood pressure in mice.
- Co-incubation increased endothelial nitric oxide synthase phosphorylation and nitric oxide release.
Conclusions:
- CD4 TChAT cells represent a distinct T-cell population involved in blood pressure regulation.
- These cells contribute to blood pressure homeostasis by promoting vasodilation via nitric oxide.
- Targeting CD4 TChAT cells may offer novel therapeutic strategies for hypertension and hypotension.
Abstract:
Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4+ T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals. Here we show that these CD4+CD44hiCD62Llo T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 TChAT). Mice lacking ChAT expression in CD4+ cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JTChAT) decreased blood pressure when infused into mice. Co-incubation of JTChAT and endothelial cells increased endothelial cell levels of phosphorylated endothelial nitric oxide synthase, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasorelaxant nitric oxide. The isolation and characterization of CD4 TChAT cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.
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