The role of CD4+CD25+ regulatory T cells in macrophage-derived foam-cell formation.
Cluster of differentiation (CD)4+CD25+ regulatory T cells (Tregs) exert a suppressive activity on atherosclerosis, but the underlying mechanism remains unclear. Here, we investigated whether and how Tregs affect macrophages foam-cell formation. Tregs were isolated by magnetic cell sorting-column and analyzed by flow cytometry. Macrophages were cultured with or without Tregs in the presence of oxidized LDL (oxLDL) for 48 h to transform foam cells. After co-culture with Tregs, macrophages showed a decrease in lipid accumulation, which was accompanied by a significantly downregulated expression of CD36 and SRA but no obvious difference in ABCA1 expression. Tregs can inhibit the proinflammatory properties of macrophages and steer macrophage differentiation toward an anti-inflammatory cytokine producing phenotype. Mechanistic studies reveal that both cell-to-cell contact and soluble factors are required for Treg-mediated suppression on macrophage foam-cell formation. Cytokines, interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta) are the key factors for these suppressive functions.
Lin
Jing
J
Department of Cardiology, Institute of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of ScienceTechnology, Wuhan, China.
Li
Ming
M
Wang
Zhixiao
Z
He
Shaolin
S
Ma
Xuming
X
Li
Dazhu
D
D000818:Animals; D001692:Biological Transport; D015704:CD4 Antigens / Q000378:metabolism*; D002454:Cell Differentiation; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D006706:Homeostasis; D007249:Inflammation / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D012995:Solubility; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism*
D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol