Regulatory T Cell Stability and Plasticity in Atherosclerosis

Cells. 2020 Dec 11;9(12):2665. doi: 10.3390/cells9122665.

Abstract

Regulatory T cells (Tregs) express the lineage-defining transcription factor FoxP3 and play crucial roles in self-tolerance and immune homeostasis. Thymic tTregs are selected based on affinity for self-antigens and are stable under most conditions. Peripheral pTregs differentiate from conventional CD4 T cells under the influence of TGF-β and other cytokines and are less stable. Treg plasticity refers to their ability to inducibly express molecules characteristic of helper CD4 T cell lineages like T-helper (Th)1, Th2, Th17 or follicular helper T cells. Plastic Tregs retain FoxP3 and are thought to be specialized regulators for "their" lineage. Unstable Tregs lose FoxP3 and switch to become exTregs, which acquire pro-inflammatory T-helper cell programs. Atherosclerosis with systemic hyperlipidemia, hypercholesterolemia, inflammatory cytokines, and local hypoxia provides an environment that is likely conducive to Tregs switching to exTregs.

Keywords: Tregs; atherosclerosis; stability.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Lineage
  • Cytokines / metabolism
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Receptors, Cell Surface
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Receptors, Cell Surface