K27Q/K29Q mutations in sphingosine kinase 1 attenuate high-fat diet induced obesity and altered glucose homeostasis in mice.

Obesity and its associated metabolic disorders are increasingly impacting public health worldwide. Sphingosine kinase 1 (Sphk1) is a critical enzyme in sphingolipid metabolism that has been implicated in various metabolic syndromes. In this study, we developed a mouse model constitutively expressing pseudoacetylated mouse Sphk1 (QSPHK1) to study its role in regulating glucose and lipid metabolism. The results showed that QSPHK1 mice gained less body weight than wide type (WT) mice on a high-fat diet, and QSPHK1 mice had improved glucolipid metabolism and insulin. Moreover, QSPHK1 mice had alleviated hepatic triglyceride accumulation and had high-fat-diet-induced hepatic steatosis that occurred as a result of reduced lipogenesis and enhanced fatty acid oxidation, which were mediated by the AMPK/ACC axis and the FGF21/adiponectin axis. Collectively, this study provided evidence that the K27Q/K29Q mutations of Sphk1 could have a protective role in preventing obesity and the related metabolic diseases. Hence, our results contribute to further understanding of the biological functions of Sphk1, which has great pharmaceutical implications.

Expansion of circulating T follicular helper cells is associated with disease progression in HIV-infected individuals.

BACKGROUND: T follicular helper (Tfh) cells within germinal centers (GC) of lymphoid tissue play an important role in HIV infection. Recently, circulating Tfh cells have been described, which share phenotypic and functional characteristics with GC Tfh cells. This study aimed to investigate the effect of HIV infection on four circulating Tfh subsets, including CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, and CD4+CXCR5+ICOS+PD-1+ cells. PATIENTS AND METHODS: Peripheral blood samples were collected from 33 HIV-infected individuals and 21 healthy controls. The frequency and absolute number of CD3, CD4 and CD8 cells were detected by flow cytometry. The frequency of circulating Tfh cell subsets was also determined by flow cytometry. The correlation between the frequency of Tfh subsets and CD4 T cells counts was assessed by Pearson correlation analysis. RESULTS: There was no significant difference in the frequency of peripheral CD4+CXCR5+ Tfh cells between HIV-infected individuals and healthy controls. However, the percentages of circulating CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, and CD4+CXCR5+ICOS+PD-1+ Tfh cells were significantly higher in individuals with HIV infection than those of healthy controls. Furthermore, the percentage of CD4+CXCR5+PD-1+ Tfh cells showed negative correlation with CD4 T cell counts in HIV-infected individuals. CONCLUSION: Our results suggested the potential involvement of circulating CD4+CXCR5+PD-1+ Tfh cells during the development of HIV infection.

Decreased frequency of circulating Th9 cells in patients with chronic hepatitis B infection.

BACKGROUND: Chronic hepatitis B (CHB) is one of the major infectious diseases in which CD4+ T helper (Th) cells play a crucial role. Th9 cells are a distinct subset of CD4+ Th cells with important physiological functions. OBJECTIVE: The study aimed to assess the potential involvement of Th9 cells in the inadequate immune response leading to chronic HBV infection. PATIENTS AND METHODS: Peripheral blood samples were collected from 22 CHB patients and 16 healthy controls (HC). The frequencies of circulating Th9, Tc9, Th1, and Tc1 cells were determined by flow cytometry. Serum levels of IL-9 and IL-10 were analyzed by ELISA. Serum biochemical indices of liver function were measured using an automated analyzers. Serum HBV DNA loads were analyzed by real-time PCR. The potential association of the frequency of Th9, Tc9, Th1 or Tc1 cells with clinical parameters was assessed. RESULTS: The frequency of circulating Th9 cells was significantly lower in CHB patients than those in HC. However, no significant differences in the frequency of Tc9, Th1 or Tc1 cells were observed between the two groups. The percentages of Th9 cells, but not Tc9 cells, were negatively correlated with HBV DNA loads, whereas the percentages of Tc1 cells were positively correlated with viral loads in CHB patients. Moreover, there was a positive correlation between serum levels of IL-9 and IL-10 and HBV DNA loads in patients with chronic HBV infection. CONCLUSION: The depletion of Th9 cells is associated with the development of chronic HBV infection.