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.

• Authors: 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
• Journal: Cell reports (Cell Rep) Vol. 24 Issue 6 Pg. 1610-1626 (08 07 2018) ISSN: 2211-1247 [Electronic] United States
• PMID: 30089270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Apelin

Topics

• Animals
• Apelin (metabolism)
• Diabetes Mellitus, Type 2 (genetics, metabolism)
• Humans
• Mice
• Neovascularization, Pathologic
• T-Lymphocytes, Regulatory (metabolism)