Regulatory T Cells Promote Apelin-Mediated Sprouting Angiogenesis in Type 2 Diabetes
Publication in refereed journal


摘要The role of CD4(+) T cells in the ischemic tissues of T2D patients remains unclear. Here, we report that T2D patients' vascular density was negatively correlated with the number of infiltrating CD4(+) T cells after ischemic injury. Th1 was the predominant subset, and Th1-derived IFN-gamma and TNF-alpha directly impaired human angiogenesis. We then blocked CD4(+) T cell infiltration into the ischemic tissues of both LePr dbldb and diet-induced obese T2D mice. Genome-wide RNA sequencing shows an increased proliferative and angiogenic capability of diabetic ECs in ischemic tissues. Moreover, wire myography shows enhanced EC function and laser Doppler imaging reveals improved post-ischemic blood reperfusion. Mechanistically, functional revascularization after CD4 coreceptor blockade was mediated by Tregs. Genetic lineage tracing via Cdh5-CreER and ApIn-CreER and coculture assays further illustrate that Tregs increased vascular density and induced de novo sprouting angiogenesis in a paracrine manner. Taken together, our results reveal that Th1 impaired while Tregs promoted functional post-ischemic revascularization in obesity and diabetes.
著者Oscar M. LEUNG, Jiatao LI, Xisheng LI, Vicken W. CHAN, Kevin Y. YANG, Manching KU, Lu JI, Hao SUN, Herman WALDMANN, Xiao Yu TIAN, Yu HUANG, James LAU, Bin ZHOU, Kathy O. LUI
期刊名稱Cell Reports
頁次1610 - 1626
關鍵詞CD4 coreceptor blockade,CD4+ regulatory T cells,vascular regeneration,vascular function,vascular inflammation apelin,type 2 diabetes
Web of Science 學科類別Cell Biology;Cell Biology

上次更新時間 2020-11-10 於 01:25