Publications (6)29.68 Total impact
-
Article: Forced miR-146a expression causes autoimmune lymphoproliferative syndrome in mice via downregulation of Fas in germinal center B cells.
[show abstract] [hide abstract]
ABSTRACT: By inhibiting target gene expression, microRNAs (miRNAs) play major roles in various physiological and pathological processes. miR-146a, a miRNA induced upon LPS stimulation and virus infection, is also highly expressed in patients with immune disorders such as rheumatoid arthritis, Sjögren's syndrome, and psoriasis. Whether the high level of miR-146a contributes to any of these pathogenesis-related processes remains unknown. To elucidate the function of miR-146a in vivo, we generated a transgenic mouse line overexpressing miR-146a. Starting at an early age, these transgenic mice developed spontaneous immune disorders mimicking human autoimmune lymphoproliferative syndrome (ALPS) with distinct manifestations, including enlarged spleens and lymph nodes, inflammatory infiltration in the livers and lungs, increased levels of double-negative T cells in peripheral blood, and increased serum IgG levels. Moreover, with the adoptive transfer approach, we found that the B cell population was the major etiological factor and that the expression of Fas, a direct target of miR-146a, was significantly dampened in transgenic germinal center B cells. These results indicate that miR-146a may be involved in the pathogenesis of ALPS by targeting Fas and may therefore serve as a novel therapeutic target.Blood 05/2013; · 9.90 Impact Factor -
Article: Increased Circulating Th22 and Th17 Cells are Associated with Tumor Progression and Patient Survival in Human Gastric Cancer.
[show abstract] [hide abstract]
ABSTRACT: Although Th22 and Th17 cells have been reported to play critical roles during autoimmunity and inflammation, information on their role in cancer-immunity is limited. In this study, we investigated clinical relevance of circulating Th22 and Th17 cells in patients with gastric cancer (GC). Using multi-color flow cytometry and PMA stimulation, we determined the levels of Th22, Th17 and Th1 cells in the peripheral blood of 32 GC patients and 19 healthy donors, and evaluated their correlations with tumor stage and overall survival. Compared with healthy donors, the frequencies of circulating CD4(+)IL-22(+) T cells, CD4(+)IL-17(+) T cells, Th22 (CD4(+)IL-22(+)IL-17(-)INF-γ(-)) cells, Th17 (CD4(+)IL-17(+)INF-γ(-)) cells were increased in patients with GC, but there was no significant differences in the frequencies of CD4(+)IFN-γ(+) T cells and Th1 (CD4(+)IL-17(-)INF-γ(+)) cells. Th22 cells showed positive correlation with Th17 cells and CD4(+)IL-17(+) T cells in patients with GC. Furthermore, the frequencies of Th22 and Th17 cells were significantly higher in stage III-IV GC patients versus stage I-II and correlated with patients' overall survival. These data suggest that circulating Th22 cells as well as Th17 cells are increased in the peripheral blood of GC patients with tumor progression, and that these cells may be promising novel clinical markers for GC.Journal of Clinical Immunology 07/2012; · 3.08 Impact Factor -
Article: Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis.
[show abstract] [hide abstract]
ABSTRACT: Increasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4+ T cells from patients with rheumatoid arthritis (RA). The expression profile of miRNAs in CD4+ T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells. miRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4+ T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-alpha), and in vitro studies showed TNF-alpha upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis. We have detected increased miR-146a in CD4+ T cells of RA patients and its close correlation with TNF-alpha levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets.Arthritis research & therapy 05/2010; 12(3):R81. · 4.27 Impact Factor -
Article: The GTPase Rab3b/3c-positive recycling vesicles are involved in cross-presentation in dendritic cells.
[show abstract] [hide abstract]
ABSTRACT: Antigen cross-presentation in dendritic cells is a complex intracellular membrane transport process, but the underlying molecular mechanisms remain to be thoroughly investigated. In this study, we examined the effect of siRNA-mediated knockdown of 57 Rab GTPases, the key regulators of membrane trafficking, on antigen cross-presentation. Twelve Rab GTPases were identified to be associated with antigen cross-presentation, and Rab3b/3c was indicated to be colocalized with MHC class I molecules at perinuclear tubular structure. Tracing with fluorescence protein-tagged beta(2)-microglobulin demonstrated that the MHC class I molecules were internalized from the plasma membrane to Rab3b/3c-positive compartments, which were also colocalized with the internalized transferrin. Moreover, depletion of Rab3b/3c strongly reduced the fast phase recycling rate of transferrin receptors. Furthermore, the Rab3b/3c-positive compartments were colocalized with a fraction of Rab27a at a juxtaposition of phagosomes. Together, these data demonstrate that Rab3b/3c-positive recycling vesicles are involved in and may constitute one of the recycling compartments in exogenous antigen cross-presentation.Proceedings of the National Academy of Sciences 09/2009; 106(37):15801-6. · 9.68 Impact Factor -
Article: Rapid generation of dendritic cell specific transgenic mice by lentiviral vectors.
[show abstract] [hide abstract]
ABSTRACT: Dendritic cell (DC) specific transgenic mice are a most important model for investigating dendritic cell functions in vivo. Recently, lentivirus mediated gene transfer has become a powerful and convenient method for generation of transgenic mice. We cloned a 1.2 kb CD11c promoter and constructed a lentiviral vector, which efficiently drove DC-specific expression in vitro. After microinjection of purified virus into the perivitelline space of single-cell embryo, more than 80% newborn mice were transgenic and 7 F0 founders were rapidly generated in 2 months. GFP was strictly expressed in CD11c+ cells in spleens, thymus and lymph nodes of the transgenic mice. Importantly, the physiological characteristics and functions of DCs in the transgenic mice were not altered by the specific expression. These results indicate that this vector could be used to rapidly prepare DC-specific transgenic mice. Thus, this lentiviral vector system may provide a convenient and useful tool to study the properties of DCs in vivo.Transgenic Research 06/2009; 18(6):921-31. · 2.75 Impact Factor -
Conference Proceeding: Digital Watermark Based on Wavelet Transform for Audio Signals.
Wavelet Analysis and Its Applications, Third International Conference on WAA, Chongqing, P. R. China 29-31 May 2003, Proceedings; 01/2003
Top co-authors
Top Journals
Institutions
-
2009–2013
-
The Third Military Medical University
Chongqing, Chongqing Shi, China
-
