No abstract

A defining feature of successful vaccination is the ability to induce long-lived antigen-specific memory cells. T follicular helper (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+ memory Tfh cells in human blood are divided into Tfh1, Tfh2 and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17 respectively. Here, we developed a new method to induce Tfh1, Tfh2 and Tfh17-like (iTfh1, iTfh2 and iTfh17) mouse cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+ central memory Tfh cells with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.

It has been observed that long noncoding RNA (lncRNA) PAPAS regulates rRNA synthesis, but its role in human diseases is unclear. Our study was carried out to investigate the role of PAPAS in hepatocellular carcinoma (HCC). In the present study, we found that PAPAS was upregulated both in plasma from patients with HCC and tumors compared with plasma from healthy people and tumor-adjacent healthy tissues. Expression levels of PAPAS in tumor tissues and plasma of patients with HCC were significantly and positively correlated. Plasma levels of PAPAS effectively distinguished stage I patients from healthy controls. MicroRNA (miR)-188-5p was downregulated in tumor tissues than in tumor-adjacent healthy tissues of patients with HCC, and was inversely correlated with PAPAS in tumor tissues but not in adjacent healthy tissues.PAPAS and miR-188-5p downregulated each other. PAPAS overexpression promoted, while miR-188-5p overexpression inhibited the HCC cell proliferation. Rescue experiment showed that miR-34a overexpression attenuated the effects of PAPAS overexpression. However, PAPAS overexpression failed to affect significantly cancer cell migration and invasion. Therefore, lncRNA PAPAS promotes HCC by interacting with miR-188-5p. K E Y W O R D Shepatocellular carcinoma, lncRNA PAPAS, miR-188-5p

Background. Henoch-Schönlein purpura (HSP) is a systemic small-vessel vasculitis caused by environmental and inherent factors. Although recent research has advanced our understanding of the role of genetic susceptibility in HSP, there are still significant gaps in our knowledge. Objectives. In this study, we aimed to explore some susceptibility genes likely associated with HSP. Material and methods. Three DNA samples from a family with HSP were used to perform whole exome sequencing with Illumina Hiseq 2500 high-throughput sequencing. The relevant single nucleotide variants (SNVs) were screened according to specific filter conditions and the screened SNVs were then verified with Sanger sequencing. The Sanger sequencing results were further screened according to available literature. Finally, candidate genes were validated in 92 samples from children with HSP, and also in 1 child with HSP from HSP family, using the polymerase chain reaction technique (PCR). Results. Our analysis revealed that the MIF gene and the MGAT5 gene related to immunity remained after screening. Among the 93 children with HSP, there were 3 patients with MIF mutations and 2 patients with MGAT5 mutations. Conclusions. Our findings are helpful for providing new methods and ideas for understanding the pathogenesis of HSP by detecting and analyzing gene mutations at the whole-exome level including multi-generation sequencing. MIF and MGAT5 may be new susceptibility loci for HSP, but their roles in the pathogenesis of HSP are worthy of further study.