Purpose: This study aims to clarify the specific mechanism by which GARP affects the atherosclerotic plaques in ApoE^−/- mice and the effect of GARP-tDC on atherosclerosis.
Methods: The mice were randomly divided into three groups: the control group, the GARP-overexpressed group and the GARP-inhibited group. After 12 weeks, all the mice were euthanized, and the specimens were collected. In vitro, experiments were conducted to observe the effect of GARP on DC phenotype and the changes of the proportion of CD4⁺CD25⁺Foxp3⁺ Treg cells when GARP-tDCs were co-cultured with CD4⁺ T cells. Furthermore, adoptive transmission of GARP-tDCs was used to observe the effect on atherosclerotic plaque in mice.
Results: The GARP-overexpressed group enhanced the biological activity of Foxp3⁺ CD4⁺CD25⁺ Tregs and resulted in increased expression of LAP in T cells. In addition, the GARP-overexpressed group significantly suppressed the function of Th1 and Th17, and decreased the secretion of INF-γ and IL-17A. Thus, GARP had a protective effect on atherosclerosis. In vitro, we found that GARP-tDC had a tolerance-inducing phenotype, and GARP-tDC also had the ability to induce tolerance when co-cultured with CD4⁺ T cells. More importantly, adoptive transmission of GARP-tDCs reduced the size of atherosclerotic plaques.
Conclusion: GARP and the GARP-tDC play protective roles in atherosclerosis. The protective effect of GARP on atherosclerosis is achieved by increasing CD4⁺CD25⁺Foxp3⁺ Treg cells and inhibiting the production of IFN-γ and IL-17A.
Keywords: GARP, Foxp3, GARP-tDC, atherosclerosis, LAP