Biomedical subjects

Yanyun Zhang

Publications and source records attributed to Yanyun Zhang.

13 recordsLinked to original sources

PubMed2025

Using homologous network to identify reassortment risk in H5Nx avian influenza viruses.

The resurgence of H5Nx reassortment has caused multiple epidemics resulting in severe disease even death in wild birds and poultry. Assessing H5Nx reassortment risk is crucial for designing targeted interventions and enhancing preparedness efforts to manage H5Nx outbreaks effectively. However, the complexity in H5Nx reassortment, driven by the diversity of influenza A viruses (IAVs) and wide range of hosts, has hindered the effective quantification of reassortment risk. In this study, we utilized a network approach to explore the reassortment history using a large-scale dataset. By inferring genomic homogeneity among IAVs, we constructed an IAVs homologous network with reassortment history embedded within it. We estimated the communities within the IAVs homologous network to represent the reassortment risk of various viruses, revealing diverse reassortment risks across different H5Nx viruses. Our analysis also identified the primary hosts contributing to reassortment: domestic poultry in China, and wild birds in North America and Europe. These primary hosts are critical targets for future H5Nx reassortment interventions. Our study provides a framework for quantifying and ranking H5Nx reassortment risk, contributing to enhanced preparedness and prevention efforts.

Animals↗

PubMed2006

Synovial autoreactive T cells in rheumatoid arthritis resist IDO-mediated inhibition.

A hallmark of T cell-mediated autoimmunity is the persistence of autoreactive T cells. However, it remains to elucidate the manner in which synovial T cells are sustained in patients with rheumatoid arthritis (RA). We found that dendritic cells (DC) and tissues from the synovial joints of RA patients expressed higher levels of IDO than DC from healthy donors. Interestingly, T cells derived from the joint synovial fluid (SF) of RA patients proliferated in response to either autologous or allogeneic IDO-positive DC, an outcome that was not affected by the addition of IDO inhibitor 1-methyl-D-tryptophan (1-MT). In contrast, addition of 1-MT to the culture stimulated with allogeneic or autologous IDO-positive DC significantly enhanced the proliferation of T cells derived from peripheral blood of healthy donors or from peripheral blood of RA patients. Furthermore, we found that functionally active tryptophanyl-tRNA-synthetase (TTS) was significantly elevated in T cells derived from the SF of RA patients, leading to enhanced storage of tryptophan in T cells and to subsequent resistance to IDO-mediated deprivation of tryptophan. The RA SF enhancement of TTS expression in T cells was blocked by mAb to IFN-gamma and TNF-alpha. These results suggest that the resistance of T cells to IDO-mediated deprivation of tryptophan represents a mechanism by which autoreactive T cells are sustained in vivo in RA patients. Specifically, blocking of the up-regulation of TTS expression in T cells presents an avenue for development of a novel therapeutic approach to treatment of RA.

Adult↗

PubMed2006

Blocking tumor necrosis factor-alpha inhibits folic acid-induced acute renal failure.

Systemic administration of mice with folic acid (FA) has been used for studying the pathogenesis of acute renal failure. However, the molecular mechanisms by which FA induces acute renal failure remain poorly understood. We found that CD-1 mice treated with FA developed acute renal failure characterized by increased blood urea nitrogen, necrosis, and apoptosis of tubular epithelial cells. Compared to control mice, tumor necrosis factor-alpha (TNF-alpha) was markedly elevated in blood and kidneys of these FA-treated mice, accompanied by markedly reduced expression of anti-apoptotic protein BclxL in their kidneys. In vivo administration of FA-treated CD-1 mice with neutralizing anti-TNF-alpha antibody restored the expression of BclxL in kidneys and inhibited the necrosis and apoptosis of renal tubular epithelial cells, leading to the amelioration of acute renal failure. In ex vivo cultures, we found that FA enhanced production of TNF-alpha, decreased expression of BclxL protein, and induced apoptosis of mouse cortical tubule (MCT) cells. Addition of neutralizing anti-TNF-alpha antibody, but not control IgG, in the cultures markedly blocked the apoptotic death of FA-treated MCT cells and restored expression of BclxL to the same levels as those MCT cells cultured in the absence of FA. All these results suggest that TNF-alpha is a critical inflammatory cytokine responsible for FA-mediated acute renal failure. Furthermore, in vivo administration of anti-TNF-alpha antibody may be proved as an effective approach for acute renal failure prevention and treatment.

Acute Kidney Injury↗

PubMed2006

Anti-P-selectin lectin-EGF domain monoclonal antibody inhibits the maturation of human immature dendritic cells.

Dendritic cells (DCs) are professional antigen-presenting cells with the ability to initiate primary T cell responses. While it is well known that inflammatory stimuli induce the functional maturation of immature DCs, whether adhesion molecule selectins regulate DC maturation is poorly understood. Using anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the adhesion of P-, E-, and L-selectin, we demonstrate herein that selectins play important role in stimulating functional maturation of immature DCs. Immature DCs are generated from human cord blood CD34+ hematopoietic stem/progenitor cells that were cultured in the presence of stem cell factor, Fms-like tyrosine-kinase-3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth factor-beta1. When stimulated with tumor necrosis factor-alpha (TNF-alpha), immature DCs differentiated into mature DCs, producing increased levels of costimulatory molecules and interleukin (IL)-12 and obtaining the ability to potently activate naïve T cells. Interestingly, in contrast to mature DCs derived from TNF-alpha-induced immature DC cultures without PsL-EGFmAb, immature DCs treated with PsL-EGFmAb for 7 days were completely blocked their maturation, as evidenced by decreased expression of costimulatory molecules CD80, CD86, and CD83, inhibited production of IL-12, and inability to activate naïve T cells in vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to be a valuable tool for the study of the molecular mechanisms of DC maturation, as well as for the prevention and treatment of DC-mediated autoimmunity.

Antibodies, Monoclonal↗

PubMed2006

Dendritic cell as therapeutic vaccines against tumors and its role in therapy for hepatocellular carcinoma.

Dendritic cells (DCs) are the most potent professional antigen-presenting cells, and capable of stimulating naïve T cells and driving primary immune responses. DCs are poised to capture antigen, migrate to draining lymphoid organs, and after a process of maturation, select antigen-specific lymphocytes to which they present the processed antigen, thereby inducing immune responses. The development of protocols for the ex vivo generation of DCs may provide a rationale for designing and developing DC-based vaccination for the treatment of tumors. There are now several strategies being applied to upload antigens to DCs and manipulate DC vaccines. DC vaccines are able to induce therapeutic and protective antitumor immunity. Numerous studies indicated that hepatocellular carcinoma (HCC) immunotherapies utilizing DC-presenting tumor-associated antigens could stimulate an antitumour T cell response leading to clinical benefit without any significant toxicity. DC-based tumor vaccines have become a novel immunoadjuvant therapy for HCC.

Animals↗

PubMed2006

Valsartan inhibited the accumulation of dendritic cells in rat fibrotic renal tissue.

To observe the accumulation of dendritic cells (DCs) in rat remnant kidney and its contribution to tubulointerstitial fibrosis, under influence of valsartan on DCs, a rat remnant kidney model was established by subtotal nephrectomy. Four experimental groups were included: normal, sham, model (SNx) and the group treated with Valsartan (SNxV). Rats were killed at week 1, 4 and 12, respectively. CD1a+CD80+ DCs were assayed by double immunostaining method and the images were analyzed with Axioplan 2 microscopy. The expressions of P-selectin, TGF-beta1, alpha-SMA, collagen III and fibronectin was analyzed by immunohistochemistry or semi-quantitative RT-PCR, and the level of tubulointerstitial firosis (TIF) was scored. CD1a+CD80+ DCs were gradually increased among renal tubules, interstitium and vessels, especially in interstitium, and the number of DCs in model group at week 12 was much more than that in model groups at week 1 or 4. The expressions of P-selectin, TGF-beta1, alpha-SMA, collagen III and fibronectin in tubulointerstitial areas and the degree of TIF was increased substantially in model group at week 12. The accumulation of DCs in interstitium was well associated with the loss of renal function and the progression of tubulointerstitial fibrosis. Valsartan treatment inhibited the local accumulation of DCs and attenuated renal tubulointerstitial damage. The local DCs accumulation was related to tubulointerstitial fibrosis and renal dysfunction following renal ablation. Blockade to angiotensin II might be a potent way to attenuate renal immuno-inflammatory injury.

Angiotensin II Type 2 Receptor Blockers↗

PubMed2006

DC-SIGN and immunoregulation.

Dendritic cells (DCs) are known to be the most powerful professional antigen-presenting cells so far. It could activate primary immune response, and also downregulate immune response. DCs have a unique character of immunoregulation. DC-SIGN, a molecule designated as CD209, is one member of the C-type lectin superfamily. It is not only a pattern recognition receptor but implicated in immunoregulation of DCs. DC-SIGN has become hotspot of recent studies because of its important role in mediating DC adhesion, migration, inflammation, activating primary T cell, triggering immune response and participating in immune escape of pathogens and tumors. These studies on DC-SIGN involved in primary and secondary immune response and relevant mechanism will certainly provide us with a new method in treating and preventing certain diseases.

Cell Adhesion Molecules↗

PubMed2005

Molecular analysis and identification of virulence gene on pR(ST98) from multi-drug resistant Salmonella typhi.

pR(ST98) is a large and conjugative resistant plasmid (R plasmid) of 98.6 mega-dalton from multi-drug resistant Salmonella typhi (S. typhi), which was classified to incompatibility group C (Inc C). It has been found that pRST98 made its host bacteria not only antibiotic resistant but also more virulent. In this study we explored the possibility of plasmid pRST98 in S. typhi carrying the Salmonella plasmid virulence gene - spv. The plasmid pRST98 was isolated, purified and then digested by nine restriction endonucleases to make the plasmid enzyme profile. Spv-specific PCR and Southern blot were applied to identify the virulence gene on pR(ST98). The amplified spv fragments spvR and spvB were cloned into pGEM-T EASY and then the DNA sequences were analysed. The fragments of pRST98 digested by endonucleases Bgl II, Pst I and Sac II were identified, which may be useful for molecular analysis and further epidemiological surveillance of pR(ST98). The results of PCR and Southern blot showed that spv homologous genetic sequence which had been found in all pathogenesis Salmonella spp. except S. typhi was also presented on pR(ST98). The ORF of spvR and spvB of pRST98 were 894 bp and 1,776 bp, respectively. They have more than 99% homology with that of spvR and spvB on virulence plasmid in S. typhmurium. The genotype research on pR(ST98) revealed that there is a plasmid carrying genes responsible for drug resistance and virulence in S. typhi. This is the first report for such kind chimerical plasmid in S. typhi.

Base Sequence↗

PubMed2004

Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules.

Recruitment of dendritic cells (DCs) to lymph nodes (LNs) is pivotal to the establishment of immune response. Whereas DCs have been proven to undergo afferent lymphatic pathway to enter LNs from peripheral tissues, a question remains if DCs also migrate into LNs directly from the circulation. Here we demonstrate that plasmacytoid DC (pDC) precursors can transmigrate across high endothelial venules (HEVs) of inflamed LNs in mice. Bacterial infection induces a significant number of pDC and myeloid DC (mDC) precursors into the circulation. Both subsets express a common set of chemokine receptors except CXCR3, display parallel mobilization into the blood, but show distinct trafficking pathway to the LNs. In a short-term homing assay, whereas mDC precursors migrate to peripheral tissues and subsequently to draining LNs, pDC precursors directly enter the LNs in a CXCL9 and E-selectin dependent manner. Tumor necrosis factor-alpha controls not only DC precursor mobilization into the blood but also chemokine up-regulation on LN HEVs. A similar trafficking pathway is observed also in viral infection, and CXCR3(-/-) mice-derived pDC precursors show defective trans-HEV migration. This study clarifies the inflammation-dependent, chemokine-driven distinct property of DC precursor trafficking.

Animals↗

PubMed2004

Mobilization of dendritic cell precursors into the circulation by administration of MIP-1alpha in mice.

BACKGROUND: Dendritic cells (DCs) play a central role in immune responses and may be useful adjuvants for tumor vaccine therapy. We previously reported that F4/80(-)B220(-)CD11c(+) DC precursors expressing the CC chemokine receptors CCR1 and CCR5 are mobilized rapidly into the circulation in mice injected with Propionibacterium acnes and are recruited into inflammatory tissue by macrophage inflammatory protein 1alpha (MIP-1alpha), which binds to CCR1 and CCR5. Here we investigate the mechanisms of DC precursor mobilization and the antitumor effect of these cells in mice. METHODS: Numbers of DC precursors in peripheral blood were determined in P. acnes-treated mice (groups of 10 C57BL/B6 [B6] wild-type mice, CCR1(-/-) mice, CCR5(-/-) mice, and B6 mice treated with antibody to MIP-1alpha or control antibody) and in B6 mice injected with recombinant MIP-1alpha. MIP-1alpha-mobilized DC precursors matured by treatment with granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor-alpha and pulsed with B16 melanoma lysates were assayed for their ability to confer protective immunity against tumor challenge in vivo and to induce cytotoxic T lymphocytes against B16 tumor cells in vitro. RESULTS: The recruitment of DC precursors into the circulation by P. acnes administration was higher in B6 mice (12.6%, 95% confidence interval [CI] = 9.1% to 16.1%) than in CCR1(-/-) (9.0%, 95% CI = 7.5% to 10.5%), CCR5(-/-) (6.3%, 95% CI = 5.2% to 7.3%), or anti-MIP-1alpha antibody-treated (6.6%, 95% CI = 5.7% to 7.5%) mice. Injection of MIP-1alpha also mobilized DC precursors into the circulation (13.1%, 95% CI = 10.8% to 15.6%). Matured MIP-1alpha-mobilized-DC precursors pulsed with B16 tumor lysates elicited B16-specific antitumor immunity in vitro and in vivo. CONCLUSIONS: MIP-1alpha and its receptors are important in recruiting DC precursors into the circulation. DC precursors mobilized rapidly by MIP-1alpha may provide sufficient useful DC precursors for DC-based vaccination in cancer treatment.

Animals↗

PubMed2004

Dendritic cells as vectors for immunotherapy of tumor and its application for gastric cancer therapy.

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells (APCs) with the ability to stimulate naive resting T cells and initiate primary immune responses. DCs are poised to capture antigen (Ag), migrate to draining lymphoid organs, and, after a process of maturation, select Ag-specific lymphocytes to which they present the processed Ag, thereby inducing immune responses. Numerous studies indicated that immunotherapies utilizing DC-presenting tumor-associated antigens can safely be administered to cancer patients and induce significant immunologic and clinical responses. Moreover, it has been demonstrated that DCs are related to clinical stage, invasion, metastasis and prognosis of gastric cancer. DC-based tumor vaccines become a new effective immunoadjuvant therapy for gastric cancer.

Animals↗

PubMed2002

Identification of CD8alpha+CD11c- lineage phenotype-negative cells in the spleen as committed precursor of CD8alpha+ dendritic cells.

CD8alpha+ dendritic cells (DCs) represent a functionally distinct DC subset in vivo, which plays a critical role in initiating various cellular immune responses. However, the committed precursor of CD8alpha+ DCs remains to be identified. We reported here that murine splenic CD8alpha+CD11c- lineage phenotype (Lin)- cells could differentiate into CD8alpha+ DCs in vivo after intravenous transplantation. Immunohistochemistry staining showed that donor-derived DCs mainly located in T-cell areas of the spleen. Functionally, these CD8alpha+CD11c-Lin- cell-derived DCs were capable of stimulating allogenic T-cell response, as well as secreting bioactive interleukin 12 p70 and interferon gamma. Freshly isolated CD8alpha+CD11c-Lin- cells expressed CC chemokine receptor (CCR)2, CCR5, and CCR7 messenger RNA, whereas CD8alpha+ DCs derived from CD8alpha+CD11c-Lin- cells further obtained the expression of CCR6 and macrophage-derived chemokine. Flow cytometry analysis showed that CD8alpha+CD11c-Lin- cells were identified in bone marrow and lymph nodes. Moreover, transplanted splenic CD8alpha+CD11c-Lin- cells could also home to thymus and lymph nodes and were capable of developing into CD8alpha+ DCs in these locations. However, CD8alpha+CD11c-Li- cells failed to differentiate into CD8alpha- DCs, T cells, natural killer cells, or other myeloid lineage cells in irradiated chimeras. Taken together, all these findings suggest that CD8alpha+CD11c-Lin- cells are a committed precursor of CD8alpha+ DCs.

Animals↗

PubMed2002

Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes.

Various immune diseases are considered to be regulated by the balance of T helper (Th)1 and Th2 subsets. Although Th lymphocytes are believed to be generated in draining lymph nodes (LNs), in vivo Th cell behaviors during Th1/Th2 polarization are largely unexplored. Using a murine granulomatous liver disease model induced by Propionibacterium acnes, we show that retention of Th1 cells in the LNs is controlled by a chemokine, CXCL10/interferon (IFN) inducible protein 10 produced by mature dendritic cells (DCs). Hepatic LN DCs preferentially produced CXCL10 to attract 5'-bromo-2'-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-gamma-producing CD4+ T cells by day 7 after antigen challenge. Blockade of CXCL10 dramatically altered the distribution of cluster-forming BrdU+CD4+ T cells. BrdU+CD4+ T cells in the hepatic LNs were selectively diminished while those in the circulation were significantly increased by treatment with anti-CXCL10 monoclonal antibody. This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-gamma leading to exacerbation of liver injury. Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses.

Animals↗