γδ T Cells Mediate Angiotensin II-Induced Hypertension and Vascular Injury
| Autor: | Tlili Barhoumi, Ernesto L. Schiffrin, Antoine Caillon, Julio C. Fraulob-Aquino, Ku-Geng Huo, Sofiane Ouerd, Peter Sinnaeve, Pierre Paradis, Muhammad Oneeb Rehman Mian |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
business.industry Vascular biology 030204 cardiovascular system & hematology Angiotensin II Pathophysiology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Blood pressure Immune system Physiology (medical) Immunology Medicine Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation. 135:2155-2162 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/circulationaha.116.027058 |
| Popis: | Background: Innate antigen-presenting cells and adaptive immune T cells have been implicated in the development of hypertension. However, the T-lymphocyte subsets involved in the pathophysiology of hypertension remain unclear. A small subset of innate-like T cells expressing the γδ T cell receptor (TCR) rather than the αβ TCR could play a role in the initiation of the immune response in hypertension. We aimed to determine whether angiotensin (Ang) II caused kinetic changes in γδ T cells; deficiency in γδ T cells blunted Ang II-induced hypertension, vascular injury, and T-cell activation; and γδ T cells are associated with human hypertension. Methods: Male C57BL/6 wild-type and Tcrδ −/− mice, which are devoid of γδ T cells, or wild-type mice injected IP with control isotype IgG or γδ T cell-depleting antibodies, were infused or not with Ang II for 3, 7, or 14 days. T-cell profiling was determined by flow cytometry, systolic blood pressure (SBP) by telemetry, and mesentery artery endothelial function by pressurized myography. TCR γ constant region gene expression levels and clinical data of a whole blood gene expression microarray study, including normotensive and hypertensive subjects, were used to demonstrate an association between γδ T cells and SBP. Results: Seven- and 14-day Ang II infusion increased γδ T-cell numbers and activation in the spleen of wild-type mice ( P P P Tcrδ −/− mice ( P P Tcrδ −/− mice ( P R 2 =0.12, P -6 ). Conclusions: γδ T cells mediate Ang II-induced SBP elevation, vascular injury, and T-cell activation in mice. γδ T cells might contribute to the development of hypertension in humans. |
| Databáze: | OpenAIRE |
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