Abstract：
: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-γ and TNF-α directly impaired human angiogenesis. We then blocked CD4+ T cell infiltration into the ischemic tissues of both Leprdb/db 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 Apln-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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Leung OM,Li J,Li X,Chan VW,Yang KY,Ku M,Ji L,Sun H,Waldmann H,Tian XY,Huang Y,Lau J,Zhou B,Lui KOdoi
10.1016/j.celrep.2018.07.019subject
Has Abstractpub_date
2018-08-07 00:00:00pages
1610-1626issue
6issn
2211-1247pii
S2211-1247(18)31109-4journal_volume
24pub_type
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