Abstract 406: Direct Angiotensin AT2-Receptor Stimulation Modifies T-Cell Differentiation
Angiotensin II is known to activate T-cells via the AT1-receptor. T-cells also possess AT2-receptors (AT2Rs). However, the functional role of AT2Rs in T-cells has not been investigated.
This study tested the hypothesis that AT2R stimulation modulates T helper (Th) cell differentiation. For this purpose, naïve T-cells were isolated from spleen and lymph nodes of C57BL/6 mice, sorted, polarized in vitro under Th0, Th1, Th17 and regulatory T-cell (Treg) conditions and simultaneously treated with the AT2R agonist C21 (1μM) or vehicle for 4 days.
24 hours after the last treatment, expression of cytokines characteristic for pro-inflammatory Th1 cells (IFNγ) and Th17 cells (IL-17), or anti-inflammatory Treg (FoxP3) were determined on mRNA (qRT-PCR) and protein (FACS analysis) level.
AT2R stimulation during polarization of naïve T-cells decreased mRNA levels of IFNγ (in TH1 polarized T-cells: 2.2±0.4x105 [vehicle] versus 0.1±0.001x105 [C21] fold increase; p<0.05), IL-17 (in TH17 polarized T-cells; 572.1±149.0 [vehicle] versus 296.1±54.4 [C21] fold increase; p<0.05) and increased mRNA levels FoxP3 (in Treg polarized T-cells: 101.9±16.1 [vehicle] versus 342.5±12.4 [C21] fold increase; p<0.05).
Similar results were obtained for protein expression of IFNγ (6.5±0.5x105 [vehicle] versus 4.0±0.7x105 [C21] cells; p<0.05), IL-17 (1.2±0.1x105 [vehicle] versus 0.9±0.1x105 [C21] cells; p=0.06 and FoxP3 (1.5±0.5x105 [vehicle] versus 3.7±0.6x105 [C21] cells; p<0.05).
From our data we conclude that AT2R stimulation modifies T-cell differentiation resulting in a composition of T-cell subsets with less pronounced pro-inflammatory properties.
Author Disclosures: B. Sehnert: None. V. Valero-Esquitino: None. D. Cirera-Salinas: None. K. Lucht: None. A. Pascual: None. C. Curato: None. R. Voll: None. T. Unger: None. U.M. Steckelings: C. Other Research Support (includes receipt of drugs, supplies, equipment or other in-kind support); Modest; receipt of drugs; Vicore Pharma.
- © 2014 by American Heart Association, Inc.