Regulatory T cells promote apelin-mediated sprouting angiogenesis in Type 2 diabetes

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Cell reports. - 24, 6 (2018) , 1610-1626, ISSN: 2211-1247

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2019
• Creator: Leung, Oscar M. ; Li, Jiatao ; Li, Xisheng ; Chan, Vicken W. ; Yang, Kevin Y. ; Ku, Manching ; Ji, Lu ; Sun, Hao ; Waldmann, Herman ; Tian, Xiao Yu ; Huang, Yu ; Lau, James ; Zhou, Bin ; Lui, Kathy O.

Further information

• DOI: 10.1016/j.celrep.2018.07.019
• URN: urn:nbn:de:bsz:25-freidok-1481462
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:57 AM CEST