@article{10.1172/jci.insight.92801, author = {Allison E. Norlander AND Mohamed A. Saleh AND Arvind K. Pandey AND Hana A. Itani AND Jing Wu AND Liang Xiao AND Jooeun Kang AND Bethany L. Dale AND Slavina B. Goleva AND Fanny Laroumanie AND Liping Du AND David G. Harrison AND Meena S. Madhur}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage}, year = {2018}, month = {11}, volume = {2}, url = {https://insight.jci.org/articles/view/92801}, abstract = {We previously showed that angiotensin II (Ang II) increases T cell production of IL-17A, and that mice deficient in IL-17A have blunted hypertension and attenuated renal and vascular dysfunction. It was recently shown that salt enhances IL-17A production from CD4+ T cells via a serum- and glucocorticoid-regulated kinase 1–dependent (SGK1-dependent) pathway. Thus, we tested the hypothesis that SGK1 signaling in T cells promotes hypertension and contributes to end-organ damage. We show that loss of T cell SGK1 results in a blunted hypertensive response to Ang II infusion by 25 mmHg. Importantly, renal and vascular inflammation is abrogated in these mice compared with control mice. Furthermore, mice lacking T cell SGK1 are protected from Ang II–induced endothelial dysfunction and renal injury. Loss of T cell SGK1 also blunts blood pressure and vascular inflammation in response to deoxycorticosterone acetate–salt (DOCA-salt) hypertension. Finally, we demonstrate that the Na+-K+-2Cl– cotransporter 1 (NKCC1) is upregulated in Th17 cells and is necessary for the salt-induced increase in SGK1 and the IL-23 receptor. These studies demonstrate that T cell SGK1 and NKCC1 may be novel therapeutic targets for the treatment of hypertension and identify a potentially new mechanism by which salt contributes to hypertension.}, number = {13}, doi = {10.1172/jci.insight.92801}, url = {https://doi.org/10.1172/jci.insight.92801}, }