Abstract 014: Loss Of Resident Innate Immune Cells Prevents Salt-Induced Increases In Renal CD8 + T Cells

Abstract

Hypertension is associated with an increase in pro-inflammatory cytokines and immune cells. Resident renal dendritic cells (rDCs) form an intricate network within the kidney. DCs can activate and recruit immune cells, as well as secrete pro-inflammatory cytokines. We previously showed that loss of renal DCs (rDC-depletion) prevents salt-sensitive hypertension and reduces intra-renal cytokines. We hypothesize that rDC-depletion alters the salt-induced immune cell profile within the kidney. To test this hypothesis, male mice lacking a functional CX 3 CR 1 chemokine receptor (CX 3 CR 1 - EGFP+/+ ) or wild-type (Wt, C57Bl6) were used. CX 3 CR 1 is required for DC localization to the kidney; thus, these mice are renal DC-depleted. Mice were fed HS (4%) or normal chow (NC) for 6 days; kidneys harvested, digested and FACS analysis performed on total immune cell populations (n=4 Wt & rDC-depleted). Cells were gated on: CD45, MHCII, Ly6C, CD11c, CD11b, CCR2, CD3, CD8, CD4, F4/F80, NK1.1, XCR1, B220, CD64, Ly6G, CD86 and CX 3 CR 1 . Data were analyzed as a percent of total immune cells (CD45 + ). HS feeding increased CD8 + T cells (7.9% ± 0.3 vs . 4.2% ± 0.4 Wt NC, ***p<0.001), while reducing classical DC1 cells (1.7% ± 0.2 vs . 3.4% ± 0.3 Wt NC, **p<0.01). This increase in CD8 + T cell population was prevented in rDC-depleted mice (4.9% ± 0.4 vs . 4.9% ± 0.5 rDC NC). We observed no CD4 + T cell differences due to either HS or with rDC-depletion. Interestingly, NK cells were increased in rDC-depleted mice at baseline (1.8 fold, ***p<0.001), and were normalized following HS feeding. In HS-fed mice, classical DC2 cells were also trending towards a decrease in rDC-depleted kidneys as compared to Wt. Here, we show that rDC-depletion prevents the salt-induced increases seen in renal CD8 + T cells. Our data previously showed early salt- and blood pressure-induced increases in cytokines, such as IL-27 and IL-6, that were similarly reduced in rDC-depleted mice. These data suggest that resident innate immune cells may be compulsory for the immediate response to increased dietary salt by increasing pro-inflammatory cytokines and recruitment of cytotoxic T cells, and may be crucial for the pathogenesis of salt-sensitive hypertension.