OX40, which belongs to the tumour necrosis factor (TNF)-receptor family, is a costimulatory receptor that can potentiate T-cell receptor signalling on the surface of T-lymphocytes. The role of OX40 in non-immune systems, particularly the cardiovascular system, has not been defined. In the present study, we observed a noticeable increase in OX40 expression during cardiac remodelling in rodent heart. In the present study, cardiac hypertrophy was induced by aortic banding (AB) in OX40 knockout (KO) mice and wild-type (WT) mice. After 8 weeks, the OX40 KO mice showed significantly attenuated cardiac hypertrophy, fibrosis and inflammation as well as preserved cardiac function compared with the WT mice. Follow-up in vitro studies suggested that CD4+ T-lymphocyte proliferation and pro-inflammatory cytokine release were significantly decreased, whereas anti-inflammatory cytokine release was considerably increased in OX40 KO mice compared with WT mice as assessed by Cell Counting Kit-8 (CCK-8) assay and ELISA. Co-culturing neonatal rat cardiomyocytes with the activated supernatant of CD4+ T-lymphocytes from OX40 KO mice reduced the hypertrophy response. Interestingly, OX40 KO mice with reconstituted CD4+ T-lymphocytes presented deteriorated cardiac remodelling. Collectively, our data indicate that OX40 regulates cardiac remodelling via the modulation of CD4+ T-lymphocytes.
OX40 regulates pressure overload-induced cardiac hypertrophy and remodelling via CD4+ T-cells
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Qing-Qing Wu, Yuan Yuan, Xiao-Han Jiang, Yang Xiao, Zheng Yang, Zhen-Guo Ma, Hai-Han Liao, Yuan Liu, Wei Chang, Zhou-Yan Bian, Qi-Zhu Tang; OX40 regulates pressure overload-induced cardiac hypertrophy and remodelling via CD4+ T-cells. Clin Sci (Lond) 1 November 2016; 130 (22): 2061–2071. doi: https://doi.org/10.1042/CS20160074
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