Cells (Dec 2020)

Regulatory T Cell Stability and Plasticity in Atherosclerosis

  • Amal J. Ali,
  • Jeffrey Makings,
  • Klaus Ley

DOI
https://doi.org/10.3390/cells9122665
Journal volume & issue
Vol. 9, no. 12
p. 2665

Abstract

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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.

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