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Type: Artigo
Title: Cd70 Exacerbates Blood Pressure Elevation And Renal Damage In Response To Repeated Hypertensive Stimuli
Author: Itani
Hana A.; Xiao
Liang; Saleh
Mohamed A.; Wu
Jing; Pilkinton
Mark A.; Dale
Bethany L.; Barbaro
Natalia R.; Foss
Jason D.; Kirabo
Annet; Montaniel
Kim R.; Norlander
Allison E.; Chen
Wei; Sato
Ryosuke; Navar
L. Gabriel; Mallal
Simon A.; Madhur
Meena S.; Bernstein
Kenneth E.; Harrison
David G.
Abstract: Accumulating evidence supports a role of adaptive immunity and particularly T cells in the pathogenesis of hypertension. Formation of memory T cells, which requires the costimulatory molecule CD70 on antigen-presenting cells, is a cardinal feature of adaptive immunity. Objective: To test the hypothesis that CD70 and immunologic memory contribute to the blood pressure elevation and renal dysfunction mediated by repeated hypertensive challenges. Methods and Results: We imposed repeated hypertensive challenges using either N-nitro-L-arginine methyl ester hydrochloride (L-NAME)/high salt or repeated angiotensin II stimulation in mice. During these challenges effector memory T cells (T-EM) accumulated in the kidney and bone marrow. In the L-NAME/high-salt model, memory T cells of the kidney were predominant sources of interferon- and interleukin-17A, known to contribute to hypertension. L-NAME/high salt increased macrophage and dendritic cell surface expression of CD70 by 3- to 5-fold. Mice lacking CD70 did not accumulate T-EM cells and did not develop hypertension to either high salt or the second angiotensin II challenge and were protected against renal damage. Bone marrow-residing T-EM cells proliferated and redistributed to the kidney in response to repeated salt feeding. Adoptively transferred T-EM cells from hypertensive mice homed to the bone marrow and spleen and expanded on salt feeding of the recipient mice. Conclusions: Our findings illustrate a previously undefined role of CD70 and long-lived T-EM cells in the development of blood pressure elevation and end-organ damage that occur on delayed exposure to mild hypertensive stimuli. Interventions to prevent repeated hypertensive surges could attenuate formation of hypertension-specific T-EM cells.
Subject: Adaptive Immunity
Bone Marrow
Immunologic Memory
Interleukin 17a
Editor: Lippincott Williams & Wilkins
Citation: Circulation Research. Lippincott Williams & Wilkins , v. 118, p. 1233 - 1243, 2016.
Rights: fechado
Identifier DOI: 10.1161/CIRCRESAHA.115.308111
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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