CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension
Background Immune cells are key regulators of the vascular inflammatory response characteristic of hypertension. In hypertensive rodents, regulatory T lymphocytes (Treg, CD4+CD25+) prevented vascular injury, cardiac damage, and endothelial dysfunction of mesenteric arteries. Whether Treg modulate th...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.118.009372 |
| _version_ | 1818775939766550528 |
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| author | M. Florencia Iulita Sonia Duchemin Diane Vallerand Tlili Barhoumi Fernando Alvarez Roman Istomine Cyril Laurent Jessica Youwakim Pierre Paradis Nathalie Arbour Ciriaco A. Piccirillo Ernesto L. Schiffrin Hélène Girouard |
| author_facet | M. Florencia Iulita Sonia Duchemin Diane Vallerand Tlili Barhoumi Fernando Alvarez Roman Istomine Cyril Laurent Jessica Youwakim Pierre Paradis Nathalie Arbour Ciriaco A. Piccirillo Ernesto L. Schiffrin Hélène Girouard |
| author_sort | M. Florencia Iulita |
| collection | DOAJ |
| description | Background Immune cells are key regulators of the vascular inflammatory response characteristic of hypertension. In hypertensive rodents, regulatory T lymphocytes (Treg, CD4+CD25+) prevented vascular injury, cardiac damage, and endothelial dysfunction of mesenteric arteries. Whether Treg modulate the cerebrovascular damage induced by hypertension is unknown. Methods and Results C57BL/6 mice were perfused with angiotensin II (Ang II; 1000 ng/kg per minute) for 14 days and adoptive transfer of 3×105 CD4+CD25+ T cells was performed via 2 intravenous injections. Control mice received a sham surgery and PBS. Treg prevented Ang II‐induced neurovascular uncoupling (P<0.05) and endothelial impairment (P<0.05), evaluated by laser Doppler flowmetry in the somatosensory cortex. The neuroprotective effect of Treg was abolished when they were isolated from mice deficient in interleukin‐10. Administration of interleukin‐10 (60 ng/d) to hypertensive mice prevented Ang II‐induced neurovascular uncoupling (P<0.05). Treg adoptive transfer also diminished systemic inflammation induced by Ang II (P<0.05), examined with a peripheral blood cytokine array. Mice receiving Ang II + Treg exhibited reduced numbers of Iba‐1+ cells in the brain cortex (P<0.05) and hippocampus (P<0.001) compared with mice infused only with Ang II. Treg prevented the increase in cerebral superoxide radicals. Overall, these effects did not appear to be directly modulated by Treg accumulating in the brain parenchyma, because only a nonsignificant number of Treg were detected in brain. Instead, Treg penetrated peripheral tissues such as the kidney, inguinal lymph nodes, and the spleen. Conclusions Treg prevent impaired cerebrovascular responses in Ang II‐induced hypertension. The neuroprotective effects of Treg involve the modulation of inflammation in the brain and periphery. |
| first_indexed | 2024-12-18T11:05:01Z |
| format | Article |
| id | doaj.art-7491ecb9dfeb40cabf315a1958cae5e8 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-18T11:05:01Z |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-7491ecb9dfeb40cabf315a1958cae5e82022-12-21T21:10:08ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802019-01-018110.1161/JAHA.118.009372CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced HypertensionM. Florencia Iulita0Sonia Duchemin1Diane Vallerand2Tlili Barhoumi3Fernando Alvarez4Roman Istomine5Cyril Laurent6Jessica Youwakim7Pierre Paradis8Nathalie Arbour9Ciriaco A. Piccirillo10Ernesto L. Schiffrin11Hélène Girouard12Department of Neurosciences Université de Montréal Montréal CanadaDepartment of Pharmacology and Physiology Université de Montréal Montréal CanadaDepartment of Pharmacology and Physiology Université de Montréal Montréal CanadaLady Davis Institute for Medical Research McGill University Montréal CanadaCentre of Excellence in Translational Immunology Research Institute of McGill University Health Centre McGill University Montréal CanadaCentre of Excellence in Translational Immunology Research Institute of McGill University Health Centre McGill University Montréal CanadaDepartment of Neurosciences Université de Montréal Montréal CanadaDepartment of Pharmacology and Physiology Université de Montréal Montréal CanadaLady Davis Institute for Medical Research McGill University Montréal CanadaDepartment of Neurosciences Université de Montréal Montréal CanadaCentre of Excellence in Translational Immunology Research Institute of McGill University Health Centre McGill University Montréal CanadaLady Davis Institute for Medical Research McGill University Montréal CanadaGroupe de recherche sur le système nerveux central (GRSNC) Université de Montréal Montréal CanadaBackground Immune cells are key regulators of the vascular inflammatory response characteristic of hypertension. In hypertensive rodents, regulatory T lymphocytes (Treg, CD4+CD25+) prevented vascular injury, cardiac damage, and endothelial dysfunction of mesenteric arteries. Whether Treg modulate the cerebrovascular damage induced by hypertension is unknown. Methods and Results C57BL/6 mice were perfused with angiotensin II (Ang II; 1000 ng/kg per minute) for 14 days and adoptive transfer of 3×105 CD4+CD25+ T cells was performed via 2 intravenous injections. Control mice received a sham surgery and PBS. Treg prevented Ang II‐induced neurovascular uncoupling (P<0.05) and endothelial impairment (P<0.05), evaluated by laser Doppler flowmetry in the somatosensory cortex. The neuroprotective effect of Treg was abolished when they were isolated from mice deficient in interleukin‐10. Administration of interleukin‐10 (60 ng/d) to hypertensive mice prevented Ang II‐induced neurovascular uncoupling (P<0.05). Treg adoptive transfer also diminished systemic inflammation induced by Ang II (P<0.05), examined with a peripheral blood cytokine array. Mice receiving Ang II + Treg exhibited reduced numbers of Iba‐1+ cells in the brain cortex (P<0.05) and hippocampus (P<0.001) compared with mice infused only with Ang II. Treg prevented the increase in cerebral superoxide radicals. Overall, these effects did not appear to be directly modulated by Treg accumulating in the brain parenchyma, because only a nonsignificant number of Treg were detected in brain. Instead, Treg penetrated peripheral tissues such as the kidney, inguinal lymph nodes, and the spleen. Conclusions Treg prevent impaired cerebrovascular responses in Ang II‐induced hypertension. The neuroprotective effects of Treg involve the modulation of inflammation in the brain and periphery.https://www.ahajournals.org/doi/10.1161/JAHA.118.009372angiotensincerebral blood flowinflammationinterleukin‐10lymphocyte |
| spellingShingle | M. Florencia Iulita Sonia Duchemin Diane Vallerand Tlili Barhoumi Fernando Alvarez Roman Istomine Cyril Laurent Jessica Youwakim Pierre Paradis Nathalie Arbour Ciriaco A. Piccirillo Ernesto L. Schiffrin Hélène Girouard CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiotensin cerebral blood flow inflammation interleukin‐10 lymphocyte |
| title | CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension |
| title_full | CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension |
| title_fullStr | CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension |
| title_full_unstemmed | CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension |
| title_short | CD4+ Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II‐Induced Hypertension |
| title_sort | cd4 regulatory t lymphocytes prevent impaired cerebral blood flow in angiotensin ii induced hypertension |
| topic | angiotensin cerebral blood flow inflammation interleukin‐10 lymphocyte |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.118.009372 |
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