Regulatory Effects of Toll-like Receptor 4 Knockout on CD4+ and CD8+ T Lymphocytes and Interleukin-17 During Myocardial Ischemia.

Toll-like receptor 4 (TLR4) is an important cellular transmembrane receptor and pattern-recognition signaling molecule for pathogens in the immune system. High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia (MI) and reperfusion through a TLR4-mediated inflammatory response. T lymphocytes are involved in MI injury; however, the specific mechanisms underlying this role remain unclear. In this study, C57BL/6 wild-type (WT) mice and TLR4 knockout mice were divided into three groups, including a normal control group, an MI group that was generated using high doses of isoproterenol (ISO), and an ISO+rHMGB1 group that was generated using a combination of ISO and recombinant HMGB1 (rHMGB1). Echocardiography, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry were used to examine each group. The results showed that rHMGB1 could further aggravate myocardial injury and increase the CD4+/CD8+ ratio and the expression level of interleukin-17 (IL-17) (p<0.05) in vivo After the TLR4 gene was knocked out, myocardial ischemic injury in mice was alleviated, and the CD4+/CD8+ ratio and IL-17 expression level were both reduced (p<0.05) in vivo. Therefore, TLR4 knockout has a protective effect against MI in mice, which may involve the regulation of the ratio between CD4+ and CD8+ T lymphocytes and of the IL-17 expression level through the HMGB1-TLR4 signaling pathway.