Search

Follicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure., T follicular helper (TFH) cell numbers are increased after vaccination and fewer of these cells might result in reduced vaccine responses. Here the authors show in mice and humans that leptin promotes TFH differentiation and that low leptin levels can impair TFH response to vaccines and virus protection in mice.

Background Chromogranin B (CgB) is a member of granin family that can be cleaved into a number of bioactive peptides. Previous studies showed that CgB is produced in cardiomyocytes and is increased in heart failure animals and patients in proportion to disease severity. Chronic total occlusion (CTO) of coronary artery leads to sustained myocardial ischemia which predisposes to adverse cardiovascular outcomes including heart failure. Purpose In this study, we sought to investigate the association between CgB and coronary collateralization formation and heart failure in patients with stable angina and CTO. Methods A total of 720 subjects with stable angina and CTO of at least one major coronary artery were enrolled in this study. CgB was assayed using an ELISA kit and the degree of coronary collaterals supplying the distal aspect of a total occlusion from the contralateral vessel was graded according to Rentrop classification. Results These was a stepwise decrease in levels of CgB with increasing Rentrop grades of coronary collateralization (P=0.001). Compared with the good collateralization (Rentrop grade 2–3) group, CgB was significantly higher in subjects with poor coronary collateralization (Rentrop grade 0–1; 1222.95 [IQR 506.24–2710.24] pg/mL vs. 776.17 [IQR 276.24–2209.39] pg/mL, P Conclusions CgB is an independent predictor of poor coronary collateralization and is related to worse heart function in patients with stable angina and CTO. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China

Background Left ventricular aneurysm (LVA), a serious complication of transmural myocardial infarction, is generally related to poor cardiovascular outcomes. The formation of LVA is essentially an inflammatory remodeling process regulated by multiple systemic and local factors. Epicardial adipose tissue (EAT), a depot of visceral adipose tissue directly overlying the myocardium, is increasingly recognized as an important immune organ by secreting a variety of bioactive adipocytokines. However, the relation of EAT to the development of LVA is still unclear. Purpose In this study, we sought to investigate the association between EAT volume and the formation of LVA in subjects with previous myocardial infarction (MI). Methods A total of 55 subjects with previous MI and the presence of LVA, and age- and sex-matched 50 subjects with previous MI but without LVA were enrolled between October 2011 and June 2019. EAT was quantified and the presence of LVA was ascertained by cardiac magnetic resonance (CMR). EAT volume was indexed to body surface area. Results In the overall population, EAT volume index was correlated positively to log-transformed N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (Pearson's r=0.332, P=0.002), and inversely to left ventricular ejection fraction (LVEF; Pearson's r=−0.240, P=0.031). The indexed EAT volume was significantly higher in subjects with than without LVA (41.10±11.73 vs. 33.25/11.70 mL/m2, P=0.003). In subjects with LVA, EAT volume index was further increased in those at older age (43.59±13.09 mL/m2 vs. 37.29±8.26 mL/m2, P=0.029) or with type 2 diabetes (43.38±12.32 mL/m2 vs. 35.20±7.67 mL/m2, P=0.013). After adjusting for sex, age and the presence of diabetes in the multivariate analysis, tertiles of EAT volume index remained significantly associated with the presence of LVA (P for trend=0. 003). Strikingly, compared to the lowest tertile (≤30.80 mL/m2), the intermediate (30.80–44.13 mL/m2) and highest (>44.13 mL/m2) tertiles of EAT volume index corresponded to 4.869– (95% CI 1.792–14.155, P=0.003) and 4.876– (95% CI, 1.787–14.206, P=0.003) increased risk for LVA. Conclusion Our study suggests that EAT volume is independently associated with the formation of LVA and reduced cardiac function after myocardial infarction. EAT in patients with or without LVA Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China