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Abstract: SA-PO756

Resident Renal Dendritic Cells Respond to Salt-Sensitive Hypertension via ToneBP, Leading to Increased Interleukin 6

Session Information

  • Hypertension and CVD: Mechanisms
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1503 Hypertension and CVD: Mechanisms


  • Yoshigi, Masaaki, University of Utah Health, Salt Lake City, Utah, United States
  • Cunliffe-Koehler, Kennedy, University of Utah Health, Salt Lake City, Utah, United States
  • Eaton, Amity F., Harvard Medical School, Boston, Massachusetts, United States
  • Srinivasan, Harini, University of Utah Health, Salt Lake City, Utah, United States
  • Brown, Dennis, Harvard Medical School, Boston, Massachusetts, United States
  • Battistone, Maria A., Harvard Medical School, Boston, Massachusetts, United States
  • Wynne, Brandi M., University of Utah Health, Salt Lake City, Utah, United States

During hypertension, dendritic cells (DCs) have been shown to activate immune cells and secrete cytokines, such as IL-6. DCs also form an intricate network within the renal cortex. Tonicity-Responsive Enhancer Binding Protein (ToneBP) is a transcriptional regulator of the cellular response to hypertoncity. ToneBP plays a role in the stress response in immune cells. We hypothesize that rDCs respond to increased sodium and salt-sensitive hypertension (SS HTN) via ToneBP, leading to increased IL-6 levels.


To test this hypothesis, mice lacking a functional CX3CR1 chemokine receptor (CX3CR1-EGFP+/+) were used. CX3CR1 is required for DC localization to the kidney; thus these mice have a renal-specific DC-depletion. Mice were subjected to increased dietary salt (HS, 4%) or normal chow, in addition to a SS HTN model; 2 weeks L-NAME followed by 1-2 weeks of wash-out and then HS chow for the remainder of the study. Pro-inflammatory cytokines using meso-scale design (MSD)(n=3-8) in serum samples. Kidney tissue was used to determine IL-6 mRNA and ToneBP levels (n=4).


Renal-dendritic cell depleted mice had a trending increase in ToneBP mRNA expression following HS (2-3weeks), which was significantly increased (2.39 fold change, p<0.0001) during SS HTN. SS HTN rDC-depleted mice had significantly reduced renal ToneBP expression (1.47 fold change, p<0.05) as compared to SS HTN Wt. When looking at IL-6 levels, we observed reductions in renal IL-6 levels (1.5 fold change) in SS HTN rDC-depleted mice compared to SS HTN Wt, with similar trending reductions in serum IL-6 levels.


Here, we show that resident renal DCs may be a primary contributor to the renal osmostic stress response by ToneBP, as shown by the considerable reductions in ToneBP mRNA following SS HTN in rDC-depleted mice. In addition, we observed similar reductions in renal and serum IL-6 levels. These data suggest that during SS HTN, DC-mediated ToneBP may contribute to the pro-inflammatory cytokine responses by innate immune cells.


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