Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase

Peder S. Olofsson; Benjamin E. Steinberg; Roozbeh Sobbi; Maureen A. Cox; Mohamed N. Ahmed; Michaela Oswald; Ferenc Szekeres; William M. Hanes; Andrea Introini; Shu Fang Liu; Nichol E. Holodick; Thomas L. Rothstein; Cecilia Lövdahl; Sangeeta S. Chavan; Huan Yang; Valentin A. Pavlov; Kristina Broliden; Ulf Andersson; Betty Diamond; Edmund J. Miller; Anders Arner; Peter K. Gregersen; Peter H. Backx; Tak W. Mak; Kevin J. Tracey

doi:10.1038/nbt.3663

Blood pressure regulation by CD4⁺ lymphocytes expressing choline acetyltransferase

Peder S. Olofsson, Benjamin E. Steinberg, Roozbeh Sobbi, Maureen A. Cox, Mohamed N. Ahmed, Michaela Oswald, Ferenc Szekeres, William M. Hanes, Andrea Introini, Shu Fang Liu, Nichol E. Holodick, Thomas L. Rothstein, Cecilia Lövdahl, Sangeeta S. Chavan, Huan Yang, Valentin A. Pavlov, Kristina Broliden, Ulf Andersson, Betty Diamond, Edmund J. MillerAnders Arner, Peter K. Gregersen, Peter H. Backx, Tak W. Mak, Kevin J. Tracey

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

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 + CD44 hi CD62L lo T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T ChAT). Mice lacking ChAT expression in CD4 + cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JT ChAT) decreased blood pressure when infused into mice. Co-incubation of JT ChAT 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 T ChAT 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.

Original language	English (US)
Pages (from-to)	1066-1071
Number of pages	6
Journal	Nature biotechnology
Volume	34
Issue number	10
DOIs	https://doi.org/10.1038/nbt.3663
State	Published - Oct 1 2016
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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Olofsson, P. S., Steinberg, B. E., Sobbi, R., Cox, M. A., Ahmed, M. N., Oswald, M., Szekeres, F., Hanes, W. M., Introini, A., Liu, S. F., Holodick, N. E., Rothstein, T. L., Lövdahl, C., Chavan, S. S., Yang, H., Pavlov, V. A., Broliden, K., Andersson, U., Diamond, B., ... Tracey, K. J. (2016). Blood pressure regulation by CD4⁺ lymphocytes expressing choline acetyltransferase. Nature biotechnology, 34(10), 1066-1071. https://doi.org/10.1038/nbt.3663

Olofsson, PS, Steinberg, BE, Sobbi, R, Cox, MA, Ahmed, MN, Oswald, M, Szekeres, F, Hanes, WM, Introini, A, Liu, SF, Holodick, NE, Rothstein, TL, Lövdahl, C, Chavan, SS, Yang, H, Pavlov, VA, Broliden, K, Andersson, U, Diamond, B, Miller, EJ, Arner, A, Gregersen, PK, Backx, PH, Mak, TW & Tracey, KJ 2016, 'Blood pressure regulation by CD4⁺ lymphocytes expressing choline acetyltransferase', Nature biotechnology, vol. 34, no. 10, pp. 1066-1071. https://doi.org/10.1038/nbt.3663

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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 + CD44 hi CD62L lo T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T ChAT). Mice lacking ChAT expression in CD4 + cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JT ChAT) decreased blood pressure when infused into mice. Co-incubation of JT ChAT 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 T ChAT 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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AU - Ahmed, Mohamed N.

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AU - Szekeres, Ferenc

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AU - Introini, Andrea

AU - Liu, Shu Fang

AU - Holodick, Nichol E.

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AU - Lövdahl, Cecilia

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AU - Yang, Huan

AU - Pavlov, Valentin A.

AU - Broliden, Kristina

AU - Andersson, Ulf

AU - Diamond, Betty

AU - Miller, Edmund J.

AU - Arner, Anders

AU - Gregersen, Peter K.

AU - Backx, Peter H.

AU - Mak, Tak W.

AU - Tracey, Kevin J.

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N2 - 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 + CD44 hi CD62L lo T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 T ChAT). Mice lacking ChAT expression in CD4 + cells have elevated arterial blood pressure, compared to littermate controls. Jurkat T cells overexpressing ChAT (JT ChAT) decreased blood pressure when infused into mice. Co-incubation of JT ChAT 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 T ChAT 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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Blood pressure regulation by CD4⁺ lymphocytes expressing choline acetyltransferase

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