Yiming Yang

East China Normal University, Shanghai, Shanghai Shi, China

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Publications (9)19.46 Total impact

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    ABSTRACT: This study investigated the priming effect of sphingosine 1-phosphate (S1P) on formyl-Met-Leu-Phe-OH (fMLP)-activated neutrophils, by specific analysis of the neutrophil respiratory burst and the signaling pathway involved in S1P activity. The neutrophil respiratory burst was indirectly detected by the cytochrome c reduction method and the dihydrorhodamine 123 staining method. The signal transduction pathways of neutrophil respiratory burst primed by S1P were detected by Western blotting. Our results showed that the S1P receptors (S1PRs) 1, 4 and 5 were the predominantly expressed neutrophil S1PRs at the cDNA level. After pretreatment with S1P, the fMLP-activated neutrophils released increased levels of superoxide anions. PI3K and Akt proteins were involved in the signaling pathway of the neutrophil respiratory burst primed by S1P. The results indicate that S1P is a new priming reagent for neutrophils and primes the respiratory burst of fMLP-activated neutrophils. S1P interacts with its receptors on neutrophils, resulting in NADPH oxidase activation by the PI3K-Akt cell signaling pathway and induction of the neutrophil respiratory burst. © 2015 S. Karger AG, Basel.
    No preview · Article · Apr 2015 · Acta Haematologica
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    Jie Yang · Yiming Yang · Huahua Fan · Hejian Zou
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    ABSTRACT: TGF-β-induced regulatory T cells (iTregs) retain Foxp3 expression and immune-suppressive activity in collagen-induced arthritis (CIA). However, the mechanisms whereby transferred iTregs suppress immune responses, particularly the interplay between iTregs and dendritic cells (DCs) in vivo, remain incompletely understood. In this study, we found that after treatment with iTregs, splenic CD11c(+)DCs, termed "DCiTreg," expressed tolerogenic phenotypes, secreted high levels of IL-10, TGF-β, and IDO, and showed potent immunosuppressive activity in vitro. After reinfusion with DCiTreg, marked antiarthritic activity improved clinical scores and histological end-points were observed. The serological levels of inflammatory cytokines and anti-CII antibodies were low and TGF-β production was high in the DCiTreg-treated group. DCiTreg also induced new iTregs in vivo. Moreover, the inhibitory activity of DCiTreg on CIA was lost following pretreatment with the inhibitor of indoleamine 2,3-dioxygenase (IDO). Collectively, these findings suggest that transferred iTregs could induce tolerogenic characteristics in splenic DCs and these cells could effectively dampen CIA in an IDO-dependent manner. Thus, the potential therapeutic effects of iTregs in CIA are likely maintained through the generation of tolerogenic DCs in vivo.
    Preview · Article · Oct 2014 · Research Journal of Immunology
  • Jie Sun · Yana Ren · Yiming Yang · Jie Yang · Rufeng Xie · Huahua Fan
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    ABSTRACT: Objective: To explore the biological characteristics and the immuno-suppression function of tolerogenic dendritic cells (tDC) induced by tacrolimus. Methods: Human monocytes derived from peripheral blood were cultured in the cGMP-compliant CellGro DC medium supplemented with GM-CSF and IL-4 to obtain dendritic cells (DCs), and 0.1 μmol/L immunosuppressive drug tacrolimus was added to the culture medium at the third and fifth day to obtain tDCs. The molecular markers of them and the livability were assayed by flow cytometry. Then the tolerance functionality of tDCs induced by many agents and these tDCs modulated allogeneic CD4 T cells was determined via CFSE proliferation assay. And the research also analyzed the biological characters and immunosuppression function of tDCs induced by tacrolimus after storing. Results: tDCs induced by tacrolimus exhibit a typical tolerogenic phenotype, whose level of costimulatory molecules CD80, CD83, CD86 and HLA-DR is (2.95 ± 1.32)%, (2.33 ± 1.60)%, (90.02 ± 7.42)% and (91.80 ± 6.18)%, respectively. It's survival rate was (85.2 ± 4.72)%. And immunosuppressive drugs didn't influence the differentiation of tDCs from monocytes. tDCs induced by immunosuppressive drugs dexamethasone, cyclosporin A and tacrolimus had lower immunogenic than control DCs as CD4+ T proliferation rate of tDCs induced by tacrolimus is 0.42% and could not primed allogeneic CD4+ T cells proliferation. Functional analyses showed that tDCs induced by tacrolimus can more effectively suppressed mature DC-induced T cell proliferation than other tDCs, whose inhibition rate can reach (67.01 ± 19.73)%. Importantly, tDCs induced by tacrolimus had phenotypical and functional stability after storing. Conclusion: tDCs induced by tacrolimus with tolerance functionality are a promising cellular therapeutic for immunomodulation.
    No preview · Article · Jun 2014 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
  • Yana Ren · Yiming Yang · Jie Yang · Rufeng Xie · Huahua Fan
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    ABSTRACT: Background: Tolerogenic dendritic cells (tDCs) can be generated in vitro by a variety of methods, including genetic or pharmacological modification. DCs that were modified by the immunosuppressive drug tacrolimus were considered to be endowed with tolerogenic functions. Study design and methods: DCs derived from human monocytes were induced in vitro by GM-CSF/IL-4 with tacrolimus. The phenotype and production of cytokines in these DCs were analyzed. The functionality of tDCs modified by tacrolimus was subsequently determined via a CFSE proliferation assay. The severity of arthritis was monitored in CIA mice after treatment with tDCs modified by tacrolimus. Results: tDCs that were modified by tacrolimus exhibited an immature phenotype. The expression of mRNA encoding IL-10 and TGF-β increased after 12h of tacrolimus stimulation, with the strongest responses being observed after 24h. The mRNA was further upregulated after tDCs were treated with LPS and IFN-γ. tDCs secreted more IL-10 and less TNF-α and had a reduced ability to activate allo-CD4(+)CD25(-) T cells. These cells suppressed mDC-induced-proliferation of CD4(+)CD25(-) T cells and produced less TNF-α and IFN-γ but increased the level of IL-10 than imDCs. Treatment of arthritic mice with tDCs modified by tacrolimus significantly inhibited the severity and progression of the disease. tDC treatment also altered the proportion of the Th1 and Th17 populations in the spleen. Conclusions: tDCs modified by tacrolimus suppressed CD4(+) T cell proliferation and inhibited collagen-induced arthritis. These results suggest the potential use of tDCs as a therapeutic approach for autoimmune arthritis.
    No preview · Article · May 2014 · International Immunopharmacology
  • Yiming Yang · Yan Yang · Jie Yang · Rufeng Xie · Yana Ren · Huahua Fan
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    ABSTRACT: Objectives: To determine the effect of nicotine stimulation on collagen-induced arthritis (CIA), especially on Th17 cells, and the influence of activated acetylcholine receptor signaling on the induction and function of in vitro-cultured Th17 cells. Methods: Mice were divided into control and experimental (nicotine) group, and PBS or nicotine-PBS was orally administered from Day 21 to Day 28. Phenotypic changes in spleen CD4(+) cells were measured by flow cytometry. α7nAChR expression in Th17 cells was detected using flow cytometry, western blotting and real-time PCR. Purified Th17 cells were further stimulated with nicotine. The cytometric bead array (CBA) assay was employed to measure TNF-α levels in mice serum and IL-17A levels in the supernatants of nicotine-treated cell cultures. Results: Compared with their counterparts, mice receiving oral nicotine showed a delayed progress of arthritis and more attenuated signs of histological changes. Moreover, serum TNFα levels were lower in the nicotine-treated group. Spleen IL-17 level of nicotine-treated mice was lower than that of the control group, and the mRNA expression of pro-inflammatory cytokines (IL-17A and IL-6) in splenocytes were also lower than that of the control group. α7nAChR expression was detected on in vitro-cultured IL-17A(+) cells. Cells treated with 10 (- 6) M nicotine expressed lower IL-17A levels. Similarly, supernatants from nicotine-treated cell cultures also showed lower IL-17A levels. Conclusions: Nicotine stimulation attenuated signs and severity of arthritis in mice. Activation of nicotine acetylcholine receptors on in vitro-cultured Th17 cells decreased their pro-inflammatory function, which may play a potential role in alleviating arthritis in mice.
    No preview · Article · Dec 2013 · Modern Rheumatology
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    Jie Yang · Yiming Yang · Yana Ren · Rufeng Xie · Hejian Zou · Huahua Fan
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    ABSTRACT: Tolerogenic dendritic cells (tDCs) are immunosuppressive cells with potent tolerogenic ability and are promising immunotherapeutic tools for treating rheumatoid arthritis (RA). However, it is currently unknown whether allogeneic tDCs (allo-tDCs) induce tolerance in RA, and whether the numbers of adoptively transferred allo-tDCs, or the requirement for pulsing with relevant auto-antigens are important. tDCs were derived from bone marrow precursors of C57BL/B6 mice, which were induced in vitro by GM-CSF, IL-10 and TGF-β1. Collagen-induced arthritis (CIA) was modeled in D1 mice by immunization with type II collagen (CII) to test the therapeutic ability of allo-tDCs against CIA. Clinical and histopathologic scores, arthritic incidence, cytokine and anti-CII antibody secretion, and CD4(+)Th subsets were analyzed. tDCs were characterized in vitro by a stable immature phonotype and a potent immunosuppressive ability. Following adoptive transfer of low doses (5×10(5)) of CII-loaded allo-tDCs, a remarkable anti-arthritic activity, improved clinical scores and histological end-points were found. Serological levels of inflammatory cytokines and anti-CII antibodies were also significantly lower in CIA mice treated with CII-pulsed allo-tDCs as compared with allo-tDCs. Moreover, treatment with allo-tDCs altered the proportion of Treg/Th17 cells. These findings suggested that allo-tDCs, especially following antigen loading, reduced the severity of CIA in a dose-dependent manner. The dampening of CIA was associated with modulated cytokine secretion, Treg/Th17 polarization and inhibition of anti-CII secretion. This study highlights the potential therapeutic utility of allo-tDCs in autoimmune arthritis and should facilitate the future design of allo-tDC immunotherapeutic strategies against RA.
    Preview · Article · Oct 2013 · PLoS ONE
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    ABSTRACT: In this study, we expanded regulatory T cells (Tregs) ex vivo from CD4(+) CD25(+) T cells from cord blood (CB) and CD4(+) CD25(+) CD127(-) T cells from adult peripheral blood (APB) and compared the suppressive functions of the newly generated Tregs. The Tregs from CB and APB were expanded either in two cycles with a polyclonal stimulus or in two cycles with an alloantigen stimulus in the first cycle and a polyclonal stimulus in the second cycle. Cell yield after Treg expansion with polyclonal stimulation was greater than that of Tregs expanded with combined alloantigen and polyclonal stimulation. The expanded Tregs expressed high levels of Foxp3, CD39 and cytotoxic T-lymphocyte antigen-4 and low levels of CD127, interleukin-2 and interferon-γ. After two cycles of expansion, the CB Tregs maintained expression of the GARP gene and showed greater suppressive function than APB Tregs. The CB Tregs that were expanded with two cycles of polyclonal stimulation suppressed not only the polyclonal antigen-driven responder T (T(resp)) cell proliferation but also the HLA mismatched dendritic cell-driven T(resp) cell proliferation. When CB and APB Tregs were expanded with a primary alloantigen stimulus followed by a secondary polyclonal stimulus, the Tregs showed a potent, antigen-specific suppressive capacity. The Tregs expanded with two cycles of polyclonal stimulation from both CB and APB alleviated acute graft-versus-host disease symptoms and prolonged survival in a murine model of graft-versus-host disease. In conclusion, CB Tregs expanded with two cycles of polyclonal stimulation had a stronger immunosuppressive function than APB Tregs. It is feasible to obtain human functional alloantigen-specific Tregs expanded ex vivo from CB and APB in large numbers.
    Preview · Article · Feb 2012 · Immunology
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    ABSTRACT: Human cord blood (CB) is a superior source of regulatory T cells (Tregs) compared with peripheral blood. Initial studies have shown that CB-derived Tregs can be effectively expanded ex vivo. However, in vitro suppressor activity of expanded CB-Tregs and their efficacy in the prevention of acute graft-versus-host disease (aGVHD) in vivo are poorly understood. In vitro, human CB CD4+CD25+ T cells expanded with anti-CD3/CD28 beads plus interleukin (IL)-2 and the phenotypes, expression of cytokines, and suppression of expanded cells were analyzed after two cycles of stimulation. In vivo, the addition of human CB-Tregs was transferred in the major histocompatibility complex-mismatched aGVHD mouse model. Survival, body weight, GVHD scoring, histopathologic specimens, serum cytokines, and Th subsets were analyzed in CB-Treg-treated mice and untreated controls. After being expanded ex vivo, human CB-derived Tregs with potent suppressor function could meet clinical demands. Up to 85% of mice with CB-Tregs treatment survived beyond Day 63 after bone marrow transplantation; however, all aGVHD mice died within 18 days. In the serum of the CB-Treg-treated mice, the production of transforming growth factor-β increased continuously, as opposed to IL-17, which decreased quickly. Consistent with the changes of cytokines, the percentage of mouse CD4+ forkhead box protein 3+ Tregs increased while that of Th17 cells decreased. Ex vivo expanded human CB-Tregs significantly prevented allogeneic aGVHD in vivo by modulating various cytokine secretion and polarizing the Treg/Th17 balance toward Treg, which suggests the potential use of expanded CB-Tregs as a therapeutic approach for GVHD.
    No preview · Article · Nov 2011 · Transfusion
  • Yana Ren · Jie Yang · Rufeng Xie · Li Gao · Yiming Yang · Huahua Fan · Kaicheng Qian
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    ABSTRACT: Exosomes are small membrane vesicles that are secreted from many cell types into various body fluids. These vesicles are thought to play a role in cell-cell interactions. Vesicles were isolated from human plasma of healthy donors by differential ultracentrifugation and ultrafiltration. The vesicles were identified by transmission electron microscopy, and their biochemical characteristics were analyzed by Western blot and flow cytometry. The immune-modulatory ability of exosomal-like vesicles was examined by incubating them with CD4+ T cells for CD4+ T-cell proliferation and apoptosis assays in vitro. Vesicles purified from human plasma displayed shapes and sizes similar to those of previously described exosomes and contained exosomes marker proteins CD63 and CD81. They also expressed molecules such as MHC Class II molecules, CD80, CD86, and the cell signal transduction molecules Wnt3a, Wnt5a, and FasL. Furthermore, functional analysis showed that allogeneic plasma exosomes restrained the survival of CD4+ T cells. Plasma exosomes can induce dose-dependent suppression of proliferation of activated CD4+ T cells, with the strongest responses induced by 500 µg/mL exosomes in vitro. Antibodies against exosomes FasL can block the activity of exosomes on CD4+ T-cell apoptosis. Moreover, three different concentrations of CD4+ T cells were inhibited by plasma exosomes and the suppressive function was not dependent on interleukin-2. Exosomes present in human plasma contain immunity-associated molecules and can induce CD4+ T-cell apoptosis in vitro. Plasma exosomes have the capacity to influence immune responses.
    No preview · Article · Nov 2010 · Transfusion