ABSTRACT
T helper 17 (Th17) cells are closely associated with the pathogenesis of several autoimmune and inflammatory diseases, and selective suppression of Th17 cell production and pathogenicity is an effective strategy for the treatment of these diseases. There is growing evidence that cellular metabolism is associated with the development of autoimmune diseases and determines the differentiation and effector functions of Th17 cells, which undergoes a metabolic reorganization during differentiation from an oxidative phosphorylation-based catabolism to a glucose-based anabolic metabolism in the initial T cells. This paper focused on reviewing recent findings regarding the importance of metabolism in T cell differentiation and autoimmune diseases, especially in Th17 cells, and discussing the regulatory mechanisms of glycolysis in Th17 cell differentiation. This review summarized the regulation of metabolism on T-cell activation and differentiation, revealed metabolic targets with specific regulation on Th17 cells, and provided reference for finding potential therapeutic targets for Th17 cell-mediated autoimmune diseases.
ABSTRACT
Objective To investigate the protective effect of dexamethasone on stress response induced by intraute-rine balloon aortic valvuloplasty (IUBAV) in a fetal lamb model. Methods Twenty-four near term twin pregnant goats were randomly assigned to control group (n=12) and dexamethasone group (intracardiac injection of dexamethasone) (n=12). Ultrasound guided IUBAV model was established. According to the combination of treatment and operation, 48 fetal lambs were divided into four groups. The following parameters were dynamically monitored by ultrasound, which were fetal and neonatal heart rate (HR), cardiac rhythm, aortic resistance index (RI) and pulsatility index (PI). On established IUBAV model, blood samples and liver tissue specimens were taken from fetal/neonatal goats for detection of blood glucose (Glu), lactate acid (LA), plasma epinephrine (E), norepinephrine (NE), cortisol (Cort), hepatic glycogen staining. Results IUBAV resulted in increased values of Glu, LA, E, NE and Cort levels, and decreased pH value, there were significant differences between pre-and 3h-post procedure (P<0.05), and significant differences were also existed in these values between pre-and 3d-post procedure (P<0.05). After administrating dexamethasone, the changes of Glu, LA, E, NE, Cort and pH levels were suppressed effectively. Fetal hepatic glycogen was consumed in large amounts due to IUBAV while recovered 3 days after IUBAV by glycogen staining. After administrating dexamethasone, hepatic glycogen consumption related to IUBAV was obviously inhibited. After IUBAV, fetal aortic RI was increased, and there was significant differences compared with pre-procedure (P<0.05). Up to 3d-post procedure, the values of RI recovered to some extent, but statistical difference was exist-ed compared with pre-procedure (P<0.05). After administrating of dexamethasone, increased aortic RI was effectively sup-pressed. Conclusions IUBAV could lead to reversible stress response and increased aortic RI in a fetal lamb model which could be alleviated by dexamethasone.