TY - JOUR
T1 - The alternation of autophagy/apoptosis in CD4+CD25+Foxp3+ Tregs on the developmental stages of atherosclerosis
AU - Tian, Yuling
AU - Liang, Xiao
AU - Wu, Yue
N1 - Publisher Copyright:
© 2017 Elsevier Masson SAS
PY - 2018/1
Y1 - 2018/1
N2 - Naturally regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses in atherosclerosis. However, the regulatory mechanism underlying Tregs upon long-term development of atherosclerosis remains unknown. Therefore, in this study, atherosclerotic model was induced in ApoE-/- mice by feeding fat-diet for 10 weeks. Quantification of atherosclerotic lesions was done by calculating the lesion size in the aortic sinus every 2 weeks. The lipid levels and inflammatory mediators were detected in serum sample. The populations of CD4+CD25+Foxp3+ Tregs were compared between ApoE-/- mice (ApoE-/-) and wild type C57BL/6 littermates (WT). The expression levels of autophagy and apoptosis signaling related regulators were determined by flow cytomery, RT-qPCR, and western blot assays in the CD4+CD25+Foxp3+ Tregs isolated from ApoE-/- and WT. We found that the sizes of plaque lesions in atherosclerotic ApoE-/- mice were larger than those in WT group during 10 weeks’ detection (all P < 0.05); Whereas, flow cytometry assay showed that the populations of CD4+CD25+Foxp3+ Tregs were significantly reduced in atherosclerotic ApoE-/- mice compared with those in corresponding WT group from the 4th weeks’ detection (all P < 0.05). The lipid accumulation and increased pro-inflammatory mediators were correlated with the developmental progression of atherosclerosis. Furthermore, compared to WT group, the functional properties of CD4+CD25+Foxp3+ Tregs from ApoE-/- mice showed a gradually decreased autophagic activity with aberrant expressions of LC3, Beclin1, ATG5, ATG7, p62 (all P < 0.05), and a gradually increased apoptotic activity with abnormal expressions of cleaved caspase 3, Bim, Bcl-2 (all P < 0.05) during the 10 weeks’ detection period. Taken together, our data demonstrated that the population of CD4+CD25+Foxp3+ Tregs was reversely correlated with plaque forming in atherosclerotic ApoE-/- mice during atherosclerosis development. And the autophagy/apoptosis-dependent Tregs might play a crucial role for the maintenance of CD4 9+CD25+Foxp3+ Tregs survival during atherosclerosis progression.
AB - Naturally regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses in atherosclerosis. However, the regulatory mechanism underlying Tregs upon long-term development of atherosclerosis remains unknown. Therefore, in this study, atherosclerotic model was induced in ApoE-/- mice by feeding fat-diet for 10 weeks. Quantification of atherosclerotic lesions was done by calculating the lesion size in the aortic sinus every 2 weeks. The lipid levels and inflammatory mediators were detected in serum sample. The populations of CD4+CD25+Foxp3+ Tregs were compared between ApoE-/- mice (ApoE-/-) and wild type C57BL/6 littermates (WT). The expression levels of autophagy and apoptosis signaling related regulators were determined by flow cytomery, RT-qPCR, and western blot assays in the CD4+CD25+Foxp3+ Tregs isolated from ApoE-/- and WT. We found that the sizes of plaque lesions in atherosclerotic ApoE-/- mice were larger than those in WT group during 10 weeks’ detection (all P < 0.05); Whereas, flow cytometry assay showed that the populations of CD4+CD25+Foxp3+ Tregs were significantly reduced in atherosclerotic ApoE-/- mice compared with those in corresponding WT group from the 4th weeks’ detection (all P < 0.05). The lipid accumulation and increased pro-inflammatory mediators were correlated with the developmental progression of atherosclerosis. Furthermore, compared to WT group, the functional properties of CD4+CD25+Foxp3+ Tregs from ApoE-/- mice showed a gradually decreased autophagic activity with aberrant expressions of LC3, Beclin1, ATG5, ATG7, p62 (all P < 0.05), and a gradually increased apoptotic activity with abnormal expressions of cleaved caspase 3, Bim, Bcl-2 (all P < 0.05) during the 10 weeks’ detection period. Taken together, our data demonstrated that the population of CD4+CD25+Foxp3+ Tregs was reversely correlated with plaque forming in atherosclerotic ApoE-/- mice during atherosclerosis development. And the autophagy/apoptosis-dependent Tregs might play a crucial role for the maintenance of CD4 9+CD25+Foxp3+ Tregs survival during atherosclerosis progression.
KW - ApoE-/-
KW - Apoptosis
KW - Atherosclerosis
KW - Autophagy
KW - Foxp3
KW - Naturally regulatory T cells
UR - https://www.scopus.com/pages/publications/85032974450
U2 - 10.1016/j.biopha.2017.11.013
DO - 10.1016/j.biopha.2017.11.013
M3 - 文章
C2 - 29136784
AN - SCOPUS:85032974450
SN - 0753-3322
VL - 97
SP - 1053
EP - 1060
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
ER -