Targeting the Th17/Treg axis: from immunological insights to therapeutic avenues in atherosclerosis

Abstract

The paradigm of atherosclerosis has evolved from a passive lipid storage disease to a dynamic immuno-inflammatory disorder, yet the precise immune checkpoints governing its progression remain a therapeutic frontier. This review dissects the yin-yang regulation exerted by CD4+ T-cell subsets, with a particular focus on the pro-inflammatory T helper 17 cells (Th17) and the immunosuppressive regulatory T cells (Tregs). We posit that the net balance of the Th17/Treg axis, rather than the isolated activity of either subset, represents an important immunomodulatory determinant that influences plaque fate—operating in concert with other established contributors to atherosclerotic progression, including hemodynamic forces, lipid burden, plaque macrophage content, and coagulation pathways. By integrating recent advances in the metabolic and transcriptional control of this equilibrium, we highlight how its disruption fuels the chronic vascular inflammation central to atherosclerosis. Moreover, we critically evaluate the translational promise of strategically recalibrating this axis, examining next-generation immunotherapies that target lineage-specific pathways to restore homeostasis. This review not only consolidates mechanistic insights but also underscores the urgent clinical potential of harnessing the Th17/Treg balance as a viable strategy to attenuate atherosclerotic disease burden.