Modulation of TIM-3 expression on T cells by interleukin-7 in patients with coronary atherosclerotic heart disease

GANG Hongsheng; PENG Dingfeng; HU Yongjun; TANG Shaoyong

doi:10.13431/j.cnki.immunol.j.20170181

Abstract：T-cell immunoglobulin and mucin domain-3 (TIM-3),which could be regulated by interleukin (IL)-7,is an important immunosuppressive molecule in both infectious and inflammatory diseases.Coronary atherosclerotic heart disease (CAHD) is also considered as a chronic inflammatory disease.Thus,the aim of current study is to investigate the expression of TIM-3 and IL-7 in patients with CAHD as well as the regulatory function of IL-7 on TIM-3,and to provide experimental evidence for elucidating the mechanism of inflammatory response in CAHD.A total of 82 patients with CAHD,including 22 of stable angina (SA),39 of unstable angina (UA),and 21 of acute myocardial infarction (AMI),as well as 20 normal controls (NC) were enrolled in this study.TIM-3 expression on T cells was measured by flow cytometry;serum IL-7 concentration was measured by enzyme linked-immunosorbent assay.Peripheral blood mononuclear cells (PBMC) were stimulated with recombinant human IL-7,and then the change of TIM-3 expression on T cells was investigated,and phosphorylated STAT-5 and SOCS3 expression were measured by Westem blotting.We found that mean fluoresent intensity value of TIM-3 expression on T cells was significantly increased in SA (118.7±16.50),UA (246.8±70.62),and AMI (332.7±55.92) when compared with NC (40.60±9.76,P＜0.001).TIM-3 expression on CD4+ T cells was significantly elevated in SA (1.32％±0.51％),UA (2.35％± 1.66％),and AMI (5.72％± 1.79％) when compared with NC (0.76％±0.24％,P＜0.05);TIM-3 expression on CD8+ T cells was also remarkably increased in UA (1.23％±0.39％) and AMI (1.64％±0.55％),but not SA (0.98％±0.35％),in comparison with NC (0.77％±0.26％).Serum concentration of IL-7 was also notably higher in AMI (66.64 pg/ml±26.38 pg/ml) than that in NC (35.17 pg/ml± 13.30 pg/ml,P=0.004 5).Recombinant human IL-7 stimulation significantly enhanced TIM-3 expression on both CD4+ and CD8+ T cells in AMI,however,only increased TIM-3 expression on CD8+ T cells in NC.Meanwhile,IL-7 stimulation also enhanced STAT-5 phosphorylation and SOCS3 expression in PBMC.The present results indicated that IL-7 can enhance TIM-3 expression,which play an important role of suppressing inflammation in CAHD to prevent the disease development.