Low-dose interleukin-2 induces clonal expansion of BACH2-repressed effector regulatory T cells following acute coronary syndrome
Targeting inflammation in atherosclerotic cardiovascular disease remains a major unmet need. Low-dose interleukin-2 (IL-2LD) selectively increases regulatory T (Treg) cell numbers in patients with coronary artery disease.
Using single-cell transcriptomics and T cell receptor analyses, Tian Zhao, Ziad Mallat and researchers from Cambridge University show that IL-2LD clonally expands effector Treg cells in patients with acute coronary syndromes. The clonally expanded Treg cells upregulate key immunosuppressive and metabolic pathways and show an increased number of predicted ligand–receptor interactions. These Treg cells also display similar predicted antigen specificities, which cluster with published sequences specific to atherosclerotic cardiovascular disease. By tracking the T cell receptors of single cells over time, they identify an inflammatory polarization of the T cell compartment after myocardial infarction, which is restrained by IL-2LD. BACH2 is identified as a repressor of the Treg effector program. However, BACH2-mediated regulation is bypassed with IL-2LD. Overall, these results lend insight into the IL-2-driven clonal expansion program in human Treg cells, with important therapeutic implications for patients with cardiovascular and other immune-mediated diseases.
Reference
Case, A.G., O’Brien, J.W., Lu, Y. et al. Low-dose interleukin-2 induces clonal expansion of BACH2-repressed effector regulatory T cells following acute coronary syndrome. Nat Cardiovasc Res4, 727–739 (2025). https://www.nature.com/articles/s44161-025-00652-y