23 These preliminary data indicated that persistent virus replication such as HBV and HCV, at least in part, may be a contributing factor to Th17 expansion
in these patients. In addition, a fraction of Th17 cells coexpressing IFN-γ, IL-4, and FoxP3 was increased in CHB patients as compared to healthy controls. Although few data define the role of these double-positive cells at present, it is likely that they represent a subset of interim cells differentiating from Th1, Th2, or Tregs. Indeed, recent studies have confirmed that Th1, Th2, and Treg cells have the potential to differentiate into Th17 cells under certain conditions.36 In CHB patients, the increased Th17-related cytokines such as IL-1β and IL-6 as well as IL-23 may facilitate Th17 differentiation and expansion. It will be of interest to elucidate the factors that selectively facilitate Th17 differentiation HM781-36B nmr and expansion in CHB patients in the future. In summary, our findings demonstrate, for the first time, that peripheral and intrahepatic
Ensartinib clinical trial Th17 cells are preferentially increased in CHB patients, which might activate mDCs and monocytes to release inflammatory cytokines during chronic HBV infection. Thus, Th17 cells may participate in the immunopathogenesis of chronic HBV infection. We thank all HBV-infected individuals and healthy participants in this study. Additional Supporting Information may be found in the online version of this article. “
“The apical sodium-dependent bile acid transporter (ASBT, SLC10A2) mediates intestinal, renal, and cholangiocyte bile acid reclamation. Transcriptional regulation of ASBT is well described, whereas information on posttranscriptional regulation is limited. Prior studies suggested that ontogeny of
ASBT is controlled in part by changes in messenger RNA (mRNA) stability. We studied the role that Hu antigen R (HuR) and tristetraprolin (TTP) play in regulating the expression of mRNA that contains the 3′ untranslated region (UTR) of rat ASBT. The 3′UTR was incorporated into an SV-40 driven luciferase Florfenicol reporter (rASBT3-luciferase) for rapid screening of regulatory effects. Silencing HuR reduced luciferase reporter activity, whereas silencing TTP enhanced luciferase activity. Conversely, overexpression of HuR enhanced rASBT3-luciferase reporter activity. The same 3′UTR fragments of rat ASBT were incorporated into a beta-globin coding mRNA construct for analysis of mRNA stability (rASBT3-βglobin). mRNA half-life was progressively shortened by the incorporation of increasing sized fragments of the 3′UTR. Silencing HuR shortened the half-life of rASBT3-βglobin containing 0.3 kb of the rat ASBT 3′UTR. Gel shift assays revealed binding of HuR and TTP to rat ASBT 3′UTR.