%0 Journal Article
%T Nox2 in regulatory T cells promotes angiotensin II每induced cardiovascular remodeling
%A Ajay M. Shah
%A Aleksar Ivetic
%A Amber Emmerson
%A Carla Ortiz
%A Giovanna Lombardi
%A Greta Sawyer
%A Heloise Mongue-Din
%A Lesley A. Smyth
%A Pablo D. Becker
%A Qi Peng
%A Raul Elgueta
%A Robert I. Lechler
%A Silvia Cellone Trevelin
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI97490
%X The superoxide-generating enzyme Nox2 contributes to hypertension and cardiovascular remodeling triggered by activation of the renin-angiotensin system. Multiple Nox2-expressing cells are implicated in angiotensin II每induced (Ang II每induced) pathophysiology, but the importance of Nox2 in leukocyte subsets is poorly understood. Here, we investigated the role of Nox2 in T cells, particularly Tregs. Mice globally deficient in Nox2 displayed increased numbers of Tregs in the heart at baseline, whereas Ang II每induced effector T cell (Teff) infiltration was inhibited. To investigate the role of Treg Nox2, we generated a mouse line with CD4-targeted Nox2 deficiency (Nox2fl/flCD4Cre+). These animals showed inhibition of Ang II每induced hypertension and cardiac remodeling related to increased tissue-resident Tregs and reduction in infiltrating Teffs, including Th17 cells. The protection in Nox2fl/flCD4Cre+ mice was reversed by anti-CD25 antibody depletion of Tregs. Mechanistically, Nox2每/y Tregs showed higher in vitro suppression of Teff proliferation than WT Tregs, increased nuclear levels of FoxP3 and NF-百B, and enhanced transcription of CD25, CD39, and CD73. Adoptive transfer of Tregs confirmed that Nox2-deficient cells had greater inhibitory effects on Ang II每induced heart remodeling than WT cells. These results identify a previously unrecognized role of Nox2 in modulating suppression of Tregs, which acts to enhance hypertension and cardiac remodeling
%U https://www.jci.org/articles/view/97490