Abstract Body: Salt-sensitive (SS) hypertension in the Dahl SS rat, a model of human hypertension, is accompanied by infiltration of immune cells into the kidney and renal damage. Previous studies have shown that genetic deletion of T cells in the Dahl SS (SS^CD247-/-) attenuates SS hypertension and renal damage. Adoptive transfer of CD4+, but not CD8+ T cells, restores the full degree of SS hypertension and renal damage in the SS^CD247-/-. To further characterize these immune cells in the Dahl SS kidney, flow cytometry and single-cell RNA sequencing (scRNASeq) analyses were performed. Remarkably, the scRNASeq identified 3 primary immune cell clusters, each expressing the Ptprc gene transcript (encoding CD45). Two clusters were defined by the common expression of CD68, including C1qc+ macrophages and Cebpb+ monocytes. The second most abundant immune cell cluster consisted of CD247+ lymphocytes. A subcluster analysis of lymphocytes identified multiple CD4+ T cell types, including Th17 cells, which increased with high salt (HS, 4.0% NaCl, n=4 pooled kidneys). These findings were confirmed by flow cytometry, which demonstrated an increase in CD4+IL17+ T cells under HS conditions (n=6/group). We thus tested the hypothesis that IL-17 Receptor C (IL-17RC) blockade will attenuate Dahl SS hypertension and renal damage. Male Dahl SS underwent a 3-week HS challenge, with blood pressure measured continuously by telemetry and urine collected weekly to assess renal damage. To inhibit the effects of IL-17, IL-17RC soluble receptor antibody (2000ng/day i.p.) or vehicle was administered to the rats every other day upon the switch to HS. IL-17RC-treated rats had significantly blunted mean arterial pressure compared to the vehicle (158±5 vs 180±10 mmHg, p<0.0001, n=4-5/group). There was also an attenuation in albumin excretion in the treated group (187±38 vs 392±81 mg/day, p=0.02). Flow cytometric analysis revealed a reduction in kidney infiltrating CD45+ immune cells (165±67 vs 539±14 cells/kidney). Overall, these data suggest that IL-17 produced by CD4+ T cells contributes to immune activation and the pathogenesis of salt-sensitive hypertension and kidney disease.