Scholarlink

<p>Targeting inflammation in atherosclerotic cardiovascular disease remains a major unmet need. Low-dose interleukin-2 (IL-2<sub>LD</sub>) selectively increases regulatory T (T<sub>reg</sub>) cell numbers in patients with coronary artery disease. Here we combine single-cell transcriptomics and T cell receptor analyses and show that IL-2<sub>LD</sub> clonally expands effector T<sub>reg</sub> cells in patients with acute coronary syndromes. The clonally expanded T<sub>reg</sub> cells upregulate key immunosuppressive and metabolic pathways and show an increased number of predicted ligand–receptor interactions. These T<sub>reg</sub> 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, we identify an inflammatory polarization of the T cell compartment after myocardial infarction, which is restrained by IL-2<sub>LD</sub>. We identify BACH2 as a repressor of the T<sub>reg</sub> effector program. However, BACH2-mediated regulation is bypassed with IL-2<sub>LD</sub>. Overall, these results lend insight into the IL-2-driven clonal expansion program in human T<sub>reg</sub> cells, with important therapeutic implications for patients with cardiovascular and other immune-mediated diseases.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Low-dose interleukin-2 induces clonal expansion of BACH2-repressed effector regulatory T cells following acute coronary syndrome

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月3日

查看全文
  • A. G. Case,
  • J. W. O’Brien,
  • Y. Lu,
  • F. T. W. Charlier,
  • X. Zhao,
  • Y. Weng,
  • L. Masters,
  • Z. K. Tuong,
  • R. Sriranjan,
  • J. Cheriyan,
  • C. Kemper,
  • M. R. Clatworthy,
  • Z. Mallat,
  • T. X. Zhao

摘要

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. Here we combine single-cell transcriptomics and T cell receptor analyses and 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, we identify an inflammatory polarization of the T cell compartment after myocardial infarction, which is restrained by IL-2LD. We identify BACH2 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.