Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, et al. Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990–2015. JAMA. 2017;317:165–82. https://doi.org/10.1001/jama.2016.19043.

Article  PubMed  Google Scholar 

He FJ, MacGregor GA. Role of salt intake in prevention of cardiovascular disease: controversies and challenges. Nat Rev Cardiol. 2018;15:371–7. https://doi.org/10.1038/s41569-018-0004-1.

Article  PubMed  Google Scholar 

• Balafa O, Kalaitzidis RG. Salt sensitivity and hypertension. J Hum Hypertens. 2021;35:184–92. https://doi.org/10.1038/s41371-020-00407-1. This review describes mechanisms of salt-sensitive hypertension.

Article  PubMed  Google Scholar 

Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, et al. Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunction. J Exp Med. 2007;204:2449–60. https://doi.org/10.1084/jem.20070657.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mattson DL, Lund H, Guo C, Rudemiller N, Geurts AM, Jacob H. Genetic mutation of recombination activating gene 1 in Dahl salt-sensitive rats attenuates hypertension and renal damage. Am J Physiol Regul Integr Comp Physiol. 2013;304:R407–14. https://doi.org/10.1152/ajpregu.00304.2012.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Crowley SD, Song Y-S, Lin EE, Griffiths R, Kim H-S, Ruiz P. Lymphocyte responses exacerbate angiotensin II-dependent hypertension. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1089-1097. https://doi.org/10.1152/ajpregu.00373.2009.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rudemiller N, Lund H, Jacob HJ, Geurts AM, Mattson DL. PhysGen Knockout Program. CD247 modulates blood pressure by altering T-lymphocyte infiltration in the kidney. Hypertension. 2014;63:559–64. https://doi.org/10.1161/hypertensionaha.113.02191.

Article  CAS  PubMed  Google Scholar 

Uchida HA, Kristo F, Rateri DL, Lu H, Charnigo R, Cassis LA, et al. Total lymphocyte deficiency attenuates AngII-induced atherosclerosis in males but not abdominal aortic aneurysms in apoE deficient mice. Atherosclerosis. 2010;211:399–403. https://doi.org/10.1016/j.atherosclerosis.2010.02.034.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Senchenkova EY, Russell J, Kurmaeva E, Ostanin D, Granger DN. Role of T lymphocytes in angiotensin II-mediated microvascular thrombosis. Hypertension. 2011;58:959–65. https://doi.org/10.1161/hypertensionaha.111.173856.

Article  CAS  PubMed  Google Scholar 

Senchenkova EY, Russell J, Yildirim A, Granger DN, Gavins FNE. Novel role of T cells and IL-6 (interleukin-6) in angiotensin II-induced microvascular dysfunction. Hypertension. 2019;73:829–38. https://doi.org/10.1161/hypertensionaha.118.12286.

Mian MOR, Barhoumi T, Briet M, Paradis P, Schiffrin EL. Deficiency of T-regulatory cells exaggerates angiotensin II-induced microvascular injury by enhancing immune responses. J Hypertens. 2016;34:97–108. https://doi.org/10.1097/hjh.0000000000000761.

Article  CAS  PubMed  Google Scholar 

Ji H, Pai AV, West CA, Wu X, Speth RC, Sandberg K. Loss of resistance to angiotensin II–Induced hypertension in the jackson laboratory recombination-activating gene null mouse on the C57BL/6J Background. hypertension. 2017;69(6):1121–7. https://doi.org/10.1161/hypertensionaha.117.09063.

Article  CAS  PubMed  Google Scholar 

• Seniuk A, Thiele JL, Stubbe A, Oser P, Rosendahl A, Bode M, et al. B6. Rag1 knockout mice generated at the Jackson Laboratory in 2009 show a robust wild-type hypertensive phenotype in response to Ang II (Angiotensin II). Hypertension. 2020;75(4):1110–6. https://doi.org/10.1161/hypertensionaha.119.13773. This article describes an unexpected outcome indicating that T-cell deficiency does not prevent Ang II-induced hypertension in RAG1−/− mice.

Article  CAS  PubMed  Google Scholar 

• Madhur MS, Kirabo A, Guzik TJ, Harrison DG. From rags to riches: moving beyond rag1 in studies of hypertension. Hypertension. 2020;75:930–34. https://doi.org/10.1161/hypertensionaha.119.14612. This review from our research group describes the divergent findings in RAG1−/− model studies.

• Bode M, Herrnstadt GR, Dreher L, Ehnert N, Kirkerup P, Lindenmeyer MT, et al. Deficiency of complement C3a and C5a receptors does not prevent angiotensin II–induced hypertension and hypertensive end-organ damage. Hypertension. 2024;81(1):138–50. https://doi.org/10.1161/hypertensionaha.123.21599. This study found that deficiency in complement C3a and C5a receptors, which are implicated in the regulation of Treg conversion, does not affect the development of hypertension or hypertensive end-organ damage in an angiotensin II-induced hypertension model.

Article  CAS  PubMed  Google Scholar 

Youn JC, Yu HT, Lim BJ, Koh MJ, Lee J, Chang DY, et al. Immunosenescent CD8+ T cells and CXC chemokine receptor type 3 chemokines are increased in human hypertension. Hypertension. 2013;62:126–33. https://doi.org/10.1161/hypertensionaha.113.00689.

Article  CAS  PubMed  Google Scholar 

Itani HA, McMaster WG Jr, Saleh MA, Nazarewicz RR, Mikolajczyk TP, Kaszuba AM, et al. Activation of human t cells in hypertension: studies of humanized mice and hypertensive humans. Hypertension. 2016;68:123–32. https://doi.org/10.1161/hypertensionaha.116.07237.

Article  CAS  PubMed  Google Scholar 

Barhoumi T, Kasal DA, Li MW, Shbat L, Laurant P, Neves MF, et al. T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011;57:469–76. https://doi.org/10.1161/hypertensionaha.110.162941.

Article  CAS  PubMed  Google Scholar 

Chan C, Sobey C, Lieu M, Ferens D, Kett M, Diep H, et al. Abstract 074: An obligatory role for B cells in the development of angiotensin II-dependent hypertension. Hypertension. 2015;66:1023–33. https://doi.org/10.1161/hypertensionaha.115.05779.

Article  CAS  PubMed  Google Scholar 

Shah KH, Shi P, Giani JF, Janjulia T, Bernstein EA, Li Y, et al. Myeloid suppressor cells accumulate and regulate blood pressure in hypertension. Circ Res. 2015;117:858–69. https://doi.org/10.1161/circresaha.115.306539.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL. Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II–infused macrophage colony-stimulating factor–deficient mice: evidence for a role in inflammation in angiotensin-induced vascular injury. Arterioscler Thromb Vasc Biol. 2005;25:2106–13. https://doi.org/10.1161/01.atv.0000181743.28028.57.

Article  PubMed  Google Scholar 

Wenzel P, Knorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S, et al. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation. 2011;124:1370–81. https://doi.org/10.1161/circulationaha.111.034470.

Article  CAS  PubMed  Google Scholar 

Krishnan SM, Ling YH, Huuskes BM, Ferens DM, Saini N, Chan CT, et al. Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension. Cardiovasc Res. 2019;115:776–87. https://doi.org/10.1093/cvr/cvy252.

Article  CAS  PubMed  Google Scholar 

Kirabo A, Fontana V, de Faria APC, Loperena R, Galindo CL, Wu J, et al. DC isoketal-modified proteins activate T cells and promote hypertension. J Clin Invest. 2014;124:4642–56. https://doi.org/10.1172/JCI74084.

Article  PubMed  PubMed Central  Google Scholar 

Barbaro NR, Foss JD, Kryshtal DO, Tsyba N, Kumaresan S, Xiao L, et al. Dendritic cell amiloride-sensitive channels mediate sodium-induced inflammation and hypertension. Cell Rep. 2017;21:1009–20. https://doi.org/10.1016/j.celrep.2017.10.002.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Van Beusecum JP, Barbaro NR, McDowell Z, Aden LA, Xiao L, Pandey AK, et al. High Salt Activates CD11c+ Antigen-Presenting Cells via SGK (Serum Glucocorticoid Kinase) 1 to Promote Renal Inflammation and Salt-Sensitive Hypertension. Hypertension. 2019;74:555–63. https://doi.org/10.1161/hypertensionaha.119.12761.

Article  PubMed  Google Scholar 

• Pitzer A, Elijovich F, Laffer CL, Ertuglu LA, Sahinoz M, Saleem M, et al. DC ENaC-Dependent inflammasome activation contributes to salt-sensitive hypertension. Circ Res. 2022;131:328–44. https://doi.org/10.1161/circresaha.122.320818. This study, performed by our research group, revealed that ENaC-mediated IsoLG production in DCs instigates the formation and activation of the NLRP3 inflammasome. This finding increases our understanding of a critical pathway in innate immunity that contributes to salt-sensitive hypertension.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hetz C, Papa FR. The unfolded protein response and cell fate control. Mol Cell. 2018;69:169–81. https://doi.org/10.1016/j.molcel.2017.06.017.

Article  CAS  PubMed  Google Scholar 

Mori K, Ma W, Gething MJ, Sambrook J. A transmembrane protein with a cdc2+/CDC28-Related kinase activity is required for signaling from the er to the nucleus. Cell. 1993;74:743–743. https://doi.org/10.1016/0092-8674(93)90521-Q.

Article  CAS  PubMed  Google Scholar 

Cox JS, Shamu CE, Walter P. Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell. 1993;73:1197–206. https://doi.org/10.1016/0092-8674(93)90648-a.

Article  CAS  PubMed  Google Scholar 

Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011;334:1081–6. https://doi.org/10.1126/science.1209038.

Article  CAS  PubMed  Google Scholar 

Smith MH, Ploegh HL, Weissman JS. Road to ruin: targeting proteins for degradation in the endoplasmic reticulum. Science. 2011;334:1086–90. https://doi.org/10.1126/science.1209235.

Article  CAS  PubMed  Google Scholar