Pathogenesis of how IL-17A produced by CD4+ T helper 17 cells result in renal and vascular dysfunction and augment angiotensin II induced hypertension

Adiba Hasnat

Introduction.  Angiotensin II hypertension is strongly linked to the immune system since many of the detrimental effects are caused by the inflammatory response mediated by immune cells such as Th17 cells7. Th17 have been shown to augment and not just be a secondary response to hypertension by promoting oxidative stress and sodium reabsorption in the kidneys4. Inflammatory cytokines such as IL-17A produced by Th17 play a major role in the pathophysiology of Angiotensin II hypertension leading to inflammation induced renal and vascular dysfunction resulting in damage to essential organs such as the heart, brain, kidneys. Methods. All studies used mouse models that were infused with angiotensin II to simulate angiogenin II induced HTN. Some of the mouse models had IL17A knock out2. Some of the mouse models were treated with SGKI inhibitor1, normal saline challenge2, and skin mesenchymal stem cells (S-MSC)3. Systolic blood pressure (SBP), serum th17 cells and serum IL17A were measured1.  Tissues samples from kidneys, heart and aorta of angII infused mice were taken and analyzed for the level of Th17 cells and IL17A using RT-PCR, flow cytometry, ELISA4. Renal transporter profiling was performed on ang II infused mice and IL17A knockout mice5. Results.  AngII infused mice treated with SGK1 inhibitor had decreased levels of Th17 and IL17A expression in renal and kidney tissue1. IL17A knock out mice had decreased SBP and higher excretion of injected sodium compared to WT mice when infused with angII2. IL17A knock out mice infused with angII had decreased renal sodium transporters compared to WT mice5. Culture of mouse distal convolute tubule cells treated with IL17A had higher sodium transporter activity than untreated cells5. AngII infused mice treated with S-MSCs had decreased SBP, serum th17, serum IL17A, aortic hypertrophy and aortic fibrosis compared to untreated mice3.  Conclusions.  Ang-II induced hypertension is highly linked to the actions of Th17 Cells and their cytokine IL-17A. IL-17A maintains elevated blood pressure in response to angiogenin II by upregulating sodium transporters5. IL-17A knock out results in loss of elevated BP response2. SGK1 causes overexpression of Th17 in response to angiotensin II1. Inhibition of SGK1 results in decreased differentiation of Th171. Skin mesenchymal stem cells decrease SBP and vascular damage due to angiotensin II by inhibiting differentiation of Th173.

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