title: Regulatory T cells prevent plaque disruption in apolipoprotein E-knockout mice.
abstract: BACKGROUND
  CD4(+)CD25(+) regulatory T cells (Tregs) have received considerable interest in atherogenesis. We hypothesized that Tregs treatment may dose-dependently stabilize atherosclerotic plaques by inhibiting inflammatory cytokine secretion and matrix metalloproteinases (MMPs) expression and enhancing P4Hα1 expression in atherosclerotic lesions.
  
  
  RESULTS
  We established a vulnerable carotid plaque model in apolipoprotein E- knockout mice (ApoE-/-). Mice were divided into control, phosphate buffered saline (PBS), small-dose Tregs, moderate-dose Tregs, large-dose Tregs and PC groups. Histopathological analysis showed that the plaque disruption rate was 50%, 50%, 43.8%, 12.5%, 12.5% and 43.8% in the control, PBS, small-dose Tregs, moderate-dose Tregs, large-dose Tregs and PC groups. Tregs treatment resulted in a significant decrease in the relative contents of macrophages and lipids and a substantial increase in those of SMCs and collagen in the carotid plaque, leading to an almost 50% reduction of plaque vulnerability index. Furthermore, Tregs treatment decreased the expression of proinflammatory cytokines, MMP-2 and MMP-9 but increased the expression of P4Hα1 both in vivo and in vitro. Most of these therapeutic effects of Tregs were found to be mediated by transforming growth factor and interleukin-10.
  
  
  CONCLUSIONS
  Adoptive transfer of Tregs dose-dependently changed plaque composition to a stable plaque phenotype and lowered the incidence of plaque disruption in ApoE-/- mice. The major mechanisms involved reduced expression of inflammatory cytokines and MMP-2 and MMP-9, and enhanced expression of P4Hα1 in the carotid plaque. Tregs may provide a novel approach to the treatment of vulnerable plaques.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Meng
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yang
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Weidong
authors.initials: W
authors.lastname: Qin
authors.forename: Guipeng
authors.initials: G
authors.lastname: An
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E
keywords: Atherosclerosis; Inflammation; Regulatory T cell; Vulnerable plaque