Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase
Autor: | William M Hanes, Sangeeta S. Chavan, Betty Diamond, Nichol E. Holodick, Anders Arner, Andrea Introini, Ferenc Szekeres, Roozbeh Sobbi, Michaela Oswald, Thomas L. Rothstein, Cecilia Lövdahl, Shu Fang Liu, Edmund J. Miller, Huan Yang, Valentin A. Pavlov, Benjamin E. Steinberg, Tak W. Mak, Peter K. Gregersen, Ulf Andersson, Kristina Broliden, Peter H. Backx, Kevin J. Tracey, Peder S. Olofsson, Maureen A. Cox, Mohamed Ahmed |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Population Biomedical Engineering Bioengineering Biology Applied Microbiology and Biotechnology Jurkat cells Nitric oxide 03 medical and health sciences chemistry.chemical_compound Immune system Internal medicine medicine education education.field_of_study Choline acetyltransferase Endothelial stem cell 030104 developmental biology Endocrinology chemistry Biochemistry Decreased blood pressure Molecular Medicine Acetylcholine Biotechnology medicine.drug |
Zdroj: | Nature Biotechnology. 34:1066-1071 |
ISSN: | 1546-1696 1087-0156 |
Popis: | 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. |
Databáze: | OpenAIRE |
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