Regulatory T CD4 + CD25+ lymphocytes increase in symptomatic carotid artery stenosis

Ann Med. 2017 Jun;49(4):283-290. doi: 10.1080/07853890.2016.1241427. Epub 2016 Dec 8.

Abstract

Background: Atherosclerosis is a multifactorial disease characterized by an immune-inflammatory remodeling of the arterial wall. Treg and Th17 subpopulations are detectable inside atherosclerotic plaque; however, their behavior in symptomatic carotid artery stenosis (CAS) is not fully elucidated. The aim of this study was to evaluate Th17 and Treg subsets and their ratio in patients affected by symptomatic and asymptomatic CAS.

Methods: 14 patients with symptomatic CAS (CAS-S group), 41 patients with asymptomatic CAS (CAS-A group), 32 subjects with traditional cardiovascular risk factors (RF group), and 10 healthy subjects (HS group) were enrolled. Th17 and Treg frequency was determined by flow cytometry and by histology and immunohistochemistry. Interleukin (IL)-10, IL-17, and metalloproteinase (MMP)-12 levels were measured by ELISA.

Results: Th17 were significantly increased in CAS-A versus RF and versus HS. Tregs were significantly increased in CAS-S versus CAS-A. Tregs/Th17 ratio was significantly reduced in CAS-A versus RF and versus HS, whereas it was significantly increased in CAS-S versus CAS-A.

Conclusions: The results of this study suggest that Th17 are related to the late stages of CAS but not to plaque instability. Moreover, Treg expansion seems to represent a specific cellular pattern displayed by patients with symptomatic CAS and associated with brain injury. KEY MESSAGES Tregs expansion seems to represent a specific cellular pattern displayed by patients with symptomatic CAS and associated with CD4+ effector depletion and brain ischemic injury. Th17 lymphocytes are related to the late stages of CAS but not to plaque instability.

Keywords: Carotid atherosclerosis; MMP-12; T lymphocyte subpopulations; cytokines.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes / metabolism*
  • Carotid Stenosis / immunology*
  • Carotid Stenosis / metabolism
  • Female
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Male
  • Matrix Metalloproteinase 12 / metabolism
  • Middle Aged
  • T-Lymphocytes, Regulatory / metabolism*
  • Th17 Cells / metabolism*

Substances

  • IL10 protein, human
  • IL2RA protein, human
  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-10
  • MMP12 protein, human
  • Matrix Metalloproteinase 12