Abstract 131: Interleukin-23 Receptor Deficiency Increased Interferon-gamma Producing T Cells And Potentiated Blood Pressure Elevation In Angiotensin II-infused Mice

Introduction: We previously demonstrated a role for γδ T cells in hypertension and vascular injury. In inflammatory conditions γδT17 are a prominent producer of IL-17A, which has been shown to contribute to hypertension. The development and expansion of γδT17 cells is regulated in part through IL-23 receptors (IL-23R). Hypothesis: We hypothesized that angiotensin (Ang) II-induced blood pressure (BP) elevation and vascular injury would be blunted in mice with dysfunctional IL-23R. Methods: Wild-type (WT) and Il23r knock-in ( Il23r gfp/gfp ) mice were infused or not with Ang II (490ng/kg/min, SC) for 7 or 14 days. BP was monitored via telemetry, mesenteric artery function and remodeling using pressurized myography, and T cell profiling in mesenteric artery perivascular adipose tissue (PVAT) by flow cytometry. Results: Il-23r gfp/gfp mice exhibited a greater BP elevation in response to Ang II than WT by day 3 (152±5 vs 144±7 mm Hg, P <0.05), which was sustained through day 9 (169±2 vs 155±5 mm Hg, P <0.05), but eventually similar to that of WT mice by the end of the Ang II infusion (167±2 vs 167±4 mm Hg). Il-23r gfp/gfp mice were not protected from vascular dysfunction and remodeling after 14 days of Ang II. Il23r gfp/gfp mice had less γδT17 cells in PVAT than WT mice (40±8 vs 108±15 cells/PVAT, P <0.05). Ang II increased interferon-γ producing γδ T cells in WT (13±3 vs 5±1 cells/PVAT, P <0.05) and Il23r gfp/gfp mice (14±3 vs 3±1 cells/PVAT, P <0.05), and interferon-γ producing CD4 + (125±27 vs 38±13 cells/PVA, P <0.05) and CD8 + T cells (76±13 vs 33±8 cells/PVA, P <0.05) only in Il23r gfp/gfp mice. Conclusion: Functional IL-23R deficiency exaggerated BP elevation during the initiation of Ang II-induced hypertension, potentially due to the increased number of interferon-γ producing T cells.