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Chu M.,Peking University | Chu M.,Key Laboratory of Medical Immunology | Xu L.,Peking University | Xu L.,Key Laboratory of Medical Immunology | And 4 more authors.
BioMed Research International | Year: 2015

Baicalin (BA) is a flavonoid compound purified from Scutellaria baicalensis Georgi and has been shown to possess a potent inhibitory activity against viruses. However, the role of BA in anti-influenza virus has not been extensively studied, and the immunological mechanism of BA in antiviral activity remains unknown. Here, we observed that BA could protect mice from infection by influenza virus A/PR/8/34 (H, associated with increasing IFN-γ production, but presented no effects in IFN-γ or IFN-γ receptor deficient mice. Further study indicated that BA could inhibit A/PR/8/34 replication through IFN-γ in human PBMC. Moreover, BA can directly induce IFN-γ production in human CD4+ and CD8+ T cells and NK cells, and activate JAK/STAT-1 signaling pathway. Collectively, BA exhibited anti-influenza virus A (H activity in vitro and in vivo as a potent inducer of IFN-γ in major IFN-γ producing cells. © 2015 Ming Chu et al. Source


Liu J.,Jishuitan Hospital | Xia M.,Peking University | Wang P.,Key Laboratory of Medical Immunology | Wang C.,Peking University | And 5 more authors.
Gene | Year: 2016

Recently, immunoglobulin (Ig) expression was reported in a variety of non-B lineage cells, including myeloid cells. We assessed whether hematopoietic stem/progenitor cells (HSC/HPCs) can express Ig. With Gene Expression Omnibus (GEO) microarray database analysis, we found that IGHM was expressed with the highest frequency and level in umbilical cord blood CD34+ HSC/HPCs, followed by IGK at, IGHE, IGHD, IGHG1, and IGHA1, while IGL at was nearly not expressed. Ig expression was further confirmed by molecular experiments and immunofluorescence. Moreover, HSC/HPCs-derived Ig displayed restricted/biased usages and VHDJH rearrangement patterns. These results suggest that Igs, especially IgM, may have a role in CD34+ HSC/HPCs function. © 2015 Elsevier B.V.. Source


Jiang D.,Peking University | Jiang D.,Key Laboratory of Medical Immunology | Ge J.,Peking University | Liao Q.,Peking University | And 10 more authors.
International Journal of Molecular Sciences | Year: 2015

The innate immune system of the skin is thought to depend largely on a multi-layered mechanical barrier supplemented by epidermis-derived antimicrobial peptides. To date, there are no reports of antimicrobial antibody secretion by the epidermis. In this study, we report the expression of functional immunoglobulin G (IgG) and immunoglobulin A (IgA), previously thought to be only produced by B cells, in normal human epidermal cells and the human keratinocyte line HaCaT. While B cells express a fully diverse Ig, epidermal cell-expressed IgG or IgA showed one or two conservative VHDJH rearrangements in each individual. These unique VDJ rearrangements in epidermal cells were found neither in the B cell-derived Ig VDJ databases published by others nor in our positive controls. IgG and IgA from epidermal cells of the same individual had different VDJ rearrangement patterns. IgG was found primarily in prickle cells, and IgA was mainly detected in basal cells. Both epidermal cell-derived IgG and IgA showed potential antibody activity by binding pathogens like Staphylococcus aureus, the most common pathogenic skin bacteria, but the microbial-binding profile was different. Our data indicates that normal human epidermal cells spontaneously express IgG and IgA, and we speculate that these Igs participate in skin innate immunity. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source


Wu W.,Peking University | Wu W.,Beijing Key Laboratory of Molecular Diagnosis on Dermatoses | Zhang R.,Peking University | Zhang R.,Beijing Key Laboratory of Molecular Diagnosis on Dermatoses | And 10 more authors.
Mycopathologia | Year: 2016

Dematiaceous fungi are a large group of pathogens that can cause a wide range of diseases in both immunocompetent and immunocompromised hosts. Based on our previous finding of caspase recruitment domain-containing protein 9 (CARD9) mutations in patients with subcutaneous phaeohyphomycosis caused by Phialophora verrucosa (P. verrucosa), we further investigated the exact role of CARD9 in the pathogenesis of phaeohyphomycosis using Card9 knockout (Card9 KO) mice. We showed that Card9 KO mice are profoundly susceptible to P. verrucosa infection compared with wild-type mice, reflected by significantly more severe footpad swelling, higher fungal burden, lower survival, and systemic dissemination. The inability of Card9 KO mice to control P. verrucosa infection was associated with lack of Th17 differentiation and reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-17A levels in footpad homogenates. In vitro experiments showed a defect of fungal conidia killing and pro-inflammatory cytokine production in Card9 KO bone marrow-derived macrophages and dendritic cells. Furthermore, ex vivo coculture and in vitro T cell differentiation assay demonstrated that Card9 signaling pathway acts indispensably on differentiation of Th17 cells. In conclusion, our findings suggest that CARD9 mediate the innate immune and Th17-mediated adaptive immune responses against dematiaceous fungal infections at the early stage of infection. © 2016 Springer Science+Business Media Dordrecht Source


Su Y.,Peking University | Su Y.,Key Laboratory of Medical Immunology | Lin Y.,Peking University | Lin Y.,Capital Medical University | And 28 more authors.
Cancer Science | Year: 2014

The CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) gene is a novel tumor suppressor with frequent epigenetic inactivation. In this study, we showed the role played by CMTM3 in gastric cancer cells as a tumor suppressor gene, and examined the correlation between CMTM3 expression and clinicopathological parameters using immunohistochemistry in gastric cancer patients with different pathological stages (n = 350). We found that CMTM3 expression was reduced or silenced by epigenetic regulation in gastric cell lines, and dramatically downregulated in primary gastric cancer tissues. Restoration of CMTM3 significantly affected migration and invasion of AGS and SGC-7901 cells (P < 0.001). In vivo experiments showed that peritoneal disseminated metastases were significantly suppressed by CMTM3 (P < 0.001). We further showed that the expression of MMP2 and the phosphorylation of Erk1/2 were decreased when CMTM3 was restored. In addition, by immunohistochemical staining, we found that the expression of CMTM3 was remarkably weaker in gastric cancer tissues than in normal mucosae (P = 0.008), and was significantly correlated with gender (P = 0.033), tumor depth (P = 0.049), stage (P = 0.021), and histological grade (P = 0.022). More importantly, CMTM3 expression was associated with prognosis in gastric cancer patients (P = 0.041), and was a significant independent prognostic indicator (hazard ratio = 0.704, 95% confidence interval, 0.498-0.994; P = 0.046). Our findings indicate that CMTM3 regulates migration and invasion of gastric cancer cells. Moreover, CMTM3 is a candidate marker for prognosis of gastric cancer in the clinic. © 2013 The Authors. Source

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