Angiotensin II-induced a steeper blood pressure elevation in IL-23 receptor-deficient mice: Role of interferon-γ-producing T cells

• Published in: Hypertension research Vol. 46; no. 1; pp. 40 - 49
• Main Authors: Shokoples, Brandon G, Comeau, Kevin, Higaki, Akinori, Ferreira, Nathanne S, Caillon, Antoine, Berillo, Olga, Oukka, Mohamed, Paradis, Pierre, Schiffrin, Ernesto L
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2023
• Subjects: Angiotensin II - pharmacology; Animals; Blood Pressure; CD8-Positive T-Lymphocytes; Hypertension; Hypertension - chemically induced; Interferon-gamma; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Interleukin - deficiency; Receptors, Interleukin - genetics; Rodents; Il23r; γδT1; Tc1; IL-17A; Th1; hypertension
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/s41440-022-01055-3

A subset of interleukin (IL)-17A-producing γδ T cells called γδT17 cells may contribute to progression of hypertension. γδT17 cell development is in part dependent upon IL-23 receptor (IL-23R) stimulation. We hypothesized that angiotensin (Ang) II-induced blood pressure (BP) elevation and vascular injury would be blunted in Il23r knock-in (Il23r ) mice deficient in functional IL-23R. To test this hypothesis, we infused wild-type (WT) and Il23r mice with Ang II (490 ng/kg/min, SC) for 7 or 14 days. We recorded BP by telemetry, assessed vascular function and remodeling using pressurized myography, and profiled T cell populations and cytokine production by flow cytometry. An additional set of Il23r mice was infused with Ang II for 7 days and injected with interferon (IFN)-γ-neutralizing or control antibodies. Il23r mice had smaller and stiffer mesenteric arteries and were not protected against Ang II-induced BP elevation. BP was higher in Il23r mice than WT mice from day 3 until day 9 of Ang II infusion. Il23r mice had less γδT17 cells and more IFN-γ-producing γδ, CD4 , and CD8 T cells than WT mice. Seven days of Ang II infusion led to increased IFN-γ-producing γδ, CD4 , and CD8 T cells in Il23r mice, whereas only IFN-γ-producing γδ T cells were increased in WT mice. Blocking IFN-γ with a neutralizing antibody reduced the pressor response to 7 days of Ang II infusion in Il23r mice. Functional IL-23R deficiency was associated with increased IFN-γ-producing T cells and exaggerated initial development of Ang II-induced hypertension, which was in part mediated by IFN-γ.