Blood pressure regulation by CD4+lymphocytes expressing choline acetyltransferase.
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+CD44hiCD62LloT 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 JTChATand 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 TChATcells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.
Center for Bioelectronic Medicine, Department of Medicine, Center for Molecular Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.|Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Peder S
PS
Olofsson
Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.|The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
Benjamin E
BE
Steinberg
Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
Roozbeh
R
Sobbi
The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
Maureen A
MA
Cox
Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Mohamed N
MN
Ahmed
Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, New York, USA.
Michaela
M
Oswald
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.|School of Health and Education, University of Skövde, Skövde, Sweden.
Ferenc
F
Szekeres
Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
William M
WM
Hanes
Department of Medicine, Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Andrea
http://orcid.org/0000-0002-9929-8964
A
Introini
Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Shu Fang
SF
Liu
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Nichol E
NE
Holodick
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Thomas L
TL
Rothstein
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Cecilia
C
Lövdahl
Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Sangeeta S
SS
Chavan
Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Huan
H
Yang
Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Valentin A
VA
Pavlov
Department of Medicine, Solna, Unit of Infectious Diseases, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Kristina
http://orcid.org/0000-0003-2224-7664
K
Broliden
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Ulf
U
Andersson
The Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Betty
http://orcid.org/0000-0002-3250-3804
B
Diamond
Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Edmund J
http://orcid.org/0000-0002-2131-0054
EJ
Miller
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Anders
A
Arner
Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research, Manhasset, New York, USA.
Peter K
PK
Gregersen
Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.|Department of Biology, York University, Toronto, Ontario, Canada.
Peter H
PH
Backx
The Campbell Family Institute for Breast Cancer Research, University Health Network, Toronto, Ontario, Canada.
Tak W
TW
Mak
Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, USA.|Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Kevin J
KJ
Tracey
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D006487:Hemostasis / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D002795:Choline O-Acetyltransferase