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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
-
Cell reports. - 24, 6 (2018) , 1610-1626, ISSN: 2211-1247
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
-
Universität
- (wann)
-
2019
- Urheber
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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.
- DOI
-
10.1016/j.celrep.2018.07.019
- URN
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urn:nbn:de:bsz:25-freidok-1481462
- Rechteinformation
-
Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
14.08.2025, 10:57 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- 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.
- Universität
Entstanden
- 2019
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