RNA Seq Analysis Reveals Metabolic and Natriuretic Pathways Regulated by Renal T Cell Infiltration

Previously, we presented work using a servo‐control system to maintain pressure to the left kidney at normotensive levels during high salt feeding. Using this approach we have demonstrated that T‐cell infiltration into the kidney during salt‐induced hypertension is a direct consequence of pressure. Further, we used RNA sequence data to detect transcriptional pathways that differ between hypertensive and normotensive kidneys, including several pathways related to immune cell migration and activation. In order to further study the interactions between T‐cells and salt‐sensitive hypertension in the Dahl S rat, we use a CD247−/− strain, which lack functional T‐cells. These rats demonstrate reduced pressures relative to wild‐type (WT) rats when fed high salt. Here, we present a study in which we adapted the servo‐control method so that the renal perfusion pressure to the left kidney of WT rats was matched on a daily basis to that of the left kidney of CD247−/− rats. This results in exposure of the left kidneys to an equivalent hypertensive response to salt. Analysis of these “pressure‐matched” kidneys therefore controls for the potentially confounding effects of pressure, and allows for a more direct comparison of tissues to reveal the effects of renal T‐cell infiltration in hypertension. Both CD247−/− and WT rats (N=4) were instrumented for servo‐control, as described previously. These rats were then fed a 4% NaCl diet to induce hypertension. Using the servo‐control system, the left kidney of the WT rats was maintained on a daily basis to match the blood pressures exhibited by the CD247−/− rats. At the conclusion of 12 days, the rat's kidneys were flushed with saline, followed by isolation of the renal medulla for RNA‐seq analysis. RNA was reverse transcribed and then sequenced on an Illumina Hi‐Seq 2500 sequencer. Data was then aligned to the RN6 genome and quantified. 2865 transcripts were found to be significantly different between the CD247−/− and WT medullas (p < 0.05). Overrepresentation analysis using DAVID found significant differences in transcripts belonging to oxidative phosphorylation (p < 8.1 * 10 −22 ), TCA cycle (p < 5.0 * 10 −9 ), collecting duct acid secretion (p < 5.7 * 10 −4 ) and aldosterone‐regulated sodium reabsorption (p < 0.013) pathways, among others. This analysis suggests that these pathways are regulated by T‐cell infiltration and activation within the renal medulla. These pathways are viable targets for the further study of the effect of immune cells on blood pressure. Support or Funding Information NIH F30HL127979 AHA 17SDG33660574 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .