Abstract 005: Loss Of Resident Renal Dendritic Cells Prevents Salt-sensitive Hypertension And Pro-inflammatory Cytokine Production

Abstract

Hypertension (HTN) is associated with an increase in pro-inflammatory cytokines. Sentinel renal dendritic cells (rDCs) form an intricate network within the kidney cortex. DCs can activate immune cells and secrete pro-inflammatory cytokines. We hypothesize that loss of renal-specific DCs (rDCs) prevents salt-sensitive hypertension (SS HTN) and reduces intra-renal chemokine and cytokine production. To test this hypothesis, male mice lacking a functional CX 3 CR 1 chemokine receptor (CX 3 CR 1 - EGFP+/+ ) or wild-type (Wt) were used. CX 3 CR 1 is required for DC localization to the kidney; thus these mice have a renal-specific DC-depletion. Mice were subjected to L-NAME (0.5mg/mL, 2 wks) and then a wash-out (1-2wks), followed by HS (4%) or normal chow (NC) for the remainder of the study. Mice were implanted with telemetry devices and mean arterial pressure (MAP) assessed. Total kidney mRNA was isolated and pro-inflammatory chemokine/cytokine levels were determined using RT-PCR (n=4-6). Wt mice exhibited a progressive increase in MAP, with rDC-depleted mice having significantly lower MAP by week 3 (121±4 vs . 114±3mmHg, *p<0.05). We observed a significant increase in renal mRNA levels of IL-27 (3.24 fold change **p<0.01) and IL-5 (3.76 fold change ****p<0.001) in Wt mice during SS HTN. Renal levels of IL-5 (1.69 fold change *p<0.05), IL-33 (0.72 fold change *p<0.05) and CXCL10 (0.52 fold change *p<0.05) were significantly reduced in rDC-depleted mice during SS HTN, as compared to Wt. When compared to NC, IL-10 levels were unchanged following SS HTN and no differences observed in rDC-depleted mice. Here, we show that rDC-depletion reduces the SS HTN response and that rDCs are necessary for the intra-renal increase of some pro-inflammatory chemokines and cytokines. These data suggest that sentinel innate immune cells within the kidney are crucial in the pathogenesis of SS HTN.