S-40-4: ANGIOTENSIN II-INDUCED BLOOD PRESSURE ELEVATION WAS POTENTIATED TOGETHER WITH INCREASES IN INTERFERON-GAMMA PRODUCING T CELLS IN INTERLEUKIN-23 RECEPTOR-DEFICIENT MICE. (January 2023)

• Record Type: Journal Article
• Authors: Paradis, Pierre; Shokoples, Brandon; Comeau, Kevin; Higaki, Akinori; Ferreira, Nathanne S; Caillon, Antoine; Berillo, Olga; Oukka, Mohamed; Schiffrin, Ernesto L
• Is Part Of: Journal of hypertension. Volume 41(2023)Supplement 1
• Page Start: e90
• Publication Date: 2023-01
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000913600.37656.24
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objectives: 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). We hypothesized that angiotensin (Ang) II-induced blood pressure (BP) elevation and vascular injury would be blunted in mice with dysfunctional IL-23R. Design and method: 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: Il23r 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). Il23r 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.