dendritic cells

摘要： Objective:To investigate the correlation of refractory rhinosinusitis by detecting the expression of dendritic cells and eosinophils infiltration in nasal mucosa.Methods:Histological staining was performed to detect eosinophils infiltration respectively in 30 normal nasal mucosa,30 chronic rhinosinusitis tissues and 30 refractory rhinosinusitis tissues,Immunohistochemistry and immunofluorescence double labeling were performed to detect the expression of CD83 and CD11c in each group,and univariate anova was used to analyze the differences among groups.The correlation between the co-expression of CD83 and CD11c and the infiltration of eosinophilic cells was measured by Pearson correlation analysis.Results:The positive expression of dendritic cells immune markers CD83 and CD11c and eosinophils infiltration of refractory rhinosinusitis was significantly increased compared with the other two groups(P<0.05).Through Pearson correlation analysisthe,correlation coefficient r between CD83 and CD11c co-expression and eosinophils infiltration in each group was positive and P<0.05,both were positively correlated.Conclusion:The number of dendritic cells in refractory rhinosinusitis increased significantly and was positively correlated with the infiltration of eosinophils,which was involved in the development of refractory rhinosinusitis.

摘要： The mononuclear phagocyte system(MPS)consists of monocytes,dendritic cells and macrophages,which play vital roles in innate immune defense against cancer.Hepatocellular carcinoma(HCC)is a complex disease that is affected or initiated by many factors,including chronic hepatitis B virus infection,hepatitis C virus infection,metabolic disorders or alcohol consumption.Liver function,tumor stage and the performance status of patients affect HCC clinical outcomes.Studies have shown that targeted treatment of tumor microenvironment disorders may improve the efficacy of HCC treatments.Cytokines derived from the innate immune response can regulate T-cell differentiation,thereby shaping adaptive immunity,which is associated with the prognosis of HCC.Therefore,it is important to elucidate the function of the MPS in the progression of HCC.In this review,we outline the impact of HCC on the MPS.We illustrate how HCC reshapes MPS cell phenotype remodeling and the production of associated cytokines and characterize the function and impairment of the MPS in HCC.

摘要： Drug-induced liver injury(DILI),which refers to liver damage caused by a drug or its metabolites,has emerged as an important cause of acute liver failure(ALF)in recent years.Chemically-induced ALF in animal models mimics the pathology of DILI in humans;thus,these models are used to study the mechanism of potentially effective treatment strategies.Mesenchymal stromal cells(MSCs)possess immunomodulatory properties,and they alleviate acute liver injury and decrease the mortality of animals with chemically-induced ALF.Here,we summarize some of the existing research on the interaction between MSCs and immune cells,and discuss the possible mechanisms underlying the immunomodulatory activity of MSCs in chemically-induced ALF.We conclude that MSCs can impact the phenotype and function of macrophages,as well as the differentiation and maturation of dendritic cells,and inhibit the proliferation and activation of T lymphocytes or B lymphocytes.MSCs also have immunomodulatory effects on the production of cytokines,such as prostaglandin E2 and tumor necrosis factor-alpha-stimulated gene 6,in animal models.Thus,MSCs have significant benefits in the treatment of chemically-induced ALF by interacting with immune cells and they may be applied to DILI in humans in the near future.

摘要： Different subpopulations of monocytes and dendritic cells(DCs)may have a key impact on the modulation of the immune response in malignancy.In this review,we summarize the monocyte and DCs heterogeneity and their function in the context of modulating the immune response in cancer.Subgroups of monocytes may play opposing roles in cancer,depending on the tumour growth and progression as well as the type of cancer.Monocytes can have pro-tumour and anti-tumour functions and can also differentiate into monocyte-derived DCs(moDCs).MoDCs have a similar antigen presentation ability as classical DCs,including cross-priming,a process by which DCs activate CD8 T-cells by crosspresenting exogenous antigens.DCs play a critical role in generating anti-tumour CD8 T-cell immunity.DCs have plastic characteristics and show distinct phenotypes depending on their mature state and depending on the influence of the tumour microenvironment.MoDCs and other DC subsets have been attracting increased interest owing to their possible beneficial effects in cancer immunotherapy.This review also highlights key strategies deploying specific DC subpopulations in combination with other therapies to enhance the anti-tumour response and summarizes the latest ongoing and completed clinical trials using DCs in lung cancer.

摘要： AIM: To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells (DCs) and cytokine-induced killer cells.METHODS: Freshly collected hepatocellular carcinoma(HCC) tumor tissues were incubated with a mixture of neuraminidase and recombinant α1,3-galactosyltransferase (α1,3GT) to synthesize α-Gal epitopes on carbohydrate chains of the glycoproteins of tumor membranes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage Ⅲ primary HCC were randomLy chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS: The evaluation demonstrated that the procedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly prolonged the survival of treated patients as compared with the controls (17.1 ± 2.01 mo vs 10.1 ± 4.5 mo,P = 0.00121). After treatment, all patients in the study group had positive delayed hyper sensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO-and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the serum.CONCLUSION: This new tumor-specific immunotherapy is safe, effective and has a great potential for the treatment of tumors.

摘要： AIM: To characterize the prevalence of subpopulations of CD4+ cells along with that of major inhibitor or stimulator cell types in therapy-nave childhood Crohn's disease (CD) and to test whether abnormalities of immune phenotype are normalized with the improvement of clinical signs and symptoms of disease. METHODS: We enrolled 26 pediatric patients with CD. 14 therapy-nave CD children; of those, 10 children remitted on conventional therapy and formed the remission group. We also tested another group of 12 chil-dren who relapsed with conventional therapy and were given infliximab; and 15 healthy children who served as controls. The prevalence of Th1 and Th2, nave and memory, activated and regulatory T cells, along with the members of innate immunity such as natural killer (NK), NK-T, myeloid and plasmocytoid dendritic cells (DCs), monocytes and Toll-like receptor (TLR)-2 and TLR-4 expression were determined in peripheral blood samples. RESULTS: Children with therapy-nave CD and those in relapse showed a decrease in Th1 cell prevalence. Simultaneously, an increased prevalence of memory and activated lymphocytes along with that of DCs and monocytes was observed. In addition, the ratio of myeloid /plasmocytoid DCs and the prevalence of TLR-2 or TLR-4 positive DCs and monocytes were also higher in therapy-nave CD than in controls. The majority of alterations diminished in remitted CD irrespective of whether remission was obtained by conventional or biological therapy. CONCLUSION: The finding that immune phenotype is normalized in remission suggests a link between immune phenotype and disease activity in childhood CD. Our observations support the involvement of members of the adaptive and innate immune systems in childhood CD.

摘要： AIM:To investigate possible differences in dendritic cells(DC)within intestinal tissue of mice before and after induction of colitis. METHODS:Mucosal DC derived from intestinal tissue,as well as from mesenteric lymph nodes and spleen,were analyzed by fluorescence activated cell sorting(FACS) analysis.Supernatants of these cells were analyzed for secretion of different pro-and anti-inflammatory cytokines. Immunohistochemistry and immunofluorescence were performed on cryosections of mucosal tissue derived from animals with colitis as well as from healthy mice. RESULTS:It was shown that DC derived from healthy intestinal lamina propria(LP)represented an immature phenotype as characterized by low-level expression of costimulatory cytokines.In contrast to DC from spleen and mesenteric lymph nodes(MLN)that secreted proinflammatory cytokines,LP-DC produced high levels of the anti-inflammatory cytokine IL-10.After induction of mu-rine colitis in a CD4 +CD62L + transfer model or in chronic Dextran sulfate sodium-colitis,a marked increase of activated CD80 + DC could be observed within the inflamed colonic tissue.Interestingly,in contrast to splenic DC,a significant population of DC within MLN and colonic LP expressed the mucosal integrin CD103 which was lost during colitis. CONCLUSION:The constitutive secretion of antiinflammatory cytokines by immature DC within the intestinal LP might regulate the homeostatic balance between mucosal immunity and tolerance.CD103 + DC could mediate this important function.

摘要： AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for cancer.Patients were allocated to receive either a placebo(group A,n=10),or a dose of 10 7 of a mixture of Bifidobacterium longum(BB536) and Lactobacillus johnsonii(La1)(group B,n=11),or the same mixture at a concentration of 10 9 (group C,n=10).Probiotics,or a placebo,were given orally 2 doses/d for 3 d before operation.The same treatment continued postoperatively from day two to day four. Stools were collected before treatment,during surgery (day 0)and 5 d after operation.During the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells(DCs)and lymphocyte subsets by surface antigen expression(flow cytometry).The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS:The three groups were balanced for baseline and surgical parameters.BB536 was never found at any time-points studied.At day 0,La1 was present in 6/10(60%)patients in either stools or by biopsy in group C,in 3/11(27.2%)in group B,and none in the placebo group(P=0.02,C vs A).There was a linear correlation between dose given and number of adher- ent La1(P=0.01).The rate of mucosal colonization by enterobacteriacae was 30%(3/10)in C,81.8%(9/11) in B and 70%(7/10)in A(P=0.03,C vs B).The Enterobacteriacae count in stools was 2.4(log10 scale) in C,4.6 in B,and 4.5 in A(P=0.07,C vs A and B). The same trend was observed for colonizing enterococ- ci.La1 was not found at day+5.We observed greater expression of CD3,CD4,CD8,and naive and memory lymphocyte subsets in group C than in group A with a dose response trend(C>B>A).Treatment didnot affect DC phenotype or activation,but after ex vivo stimulation with lipopolysaccharides,groups C and B had a lower proliferation rate compared to group A (P=0.04).Moreover,dendritic phenotypes CD83-123, CD83-HLADR,and CD83-11c(markers of activation) were significantly less expressed in patients colonized with La1(P=0.03 vs not colonized). CONCLUSION:La1,but not BB536,adheres to the colonic mucosa,and affects intestinal microbiota byreducing the concentration of pathogens and modulates local immunity.

摘要： The dendritic cell vaccine is a treatment vaccine with potent clinical applications.Functional cytokines can enhance dendritic cell anti-tumor immune responses.This experiment was conducted to study the effects of bone marrow-derived dendritic cells (BM-DCs) modified with genes encoding murine interleukin-23 (IL-23) on murine pancreatic carcinoma,and effects of the treatment of pancreatic carcinoma with β-elemene combined with IL-23-modified den dritic cell vaccine.The mttrine IL-23 cDNA was sub-cloned into a dual-expression vector.DCs were pulsed with tumor cell lysate after being modified wth IL-23.Mice were divided into groups which were injected with IL-23-transduced DC vaccine,non-transduced DC vaccine and sodium respectively.The preventive immune and immunotherapeutic effects of DC vaccines on mice and cytokine release in vivo were then assessed.Results showed inhibitory effects on tumor cells and increased survival time in the experimental group treated with the vaccine combined with β-elemene.The IL-23 protein apparently increases the antigen presenting ability of DCs.After injection with DC vaccines,IFN-γ production in the treatment group was significantly increased as compared with that in the control group (P ＜ 0.01),and IL-4 production was decreased as compared with that in the control group (P＜0.05).Tumor size was obviously reduced,and survival time clearly prolonged in the group with β-elemene combined with DC vaccine,in comparison to the other treatment groups and the control (P＜0.01).IL-23-modified dendritic cell vaccines enhance specific Th1-type and cytotoxic T lymphocyte (CTL) responses against pancreatic carcinoma cells,and induce not only auto-immune ability but also preventive immunity against pancreatic carcinoma implanted in mice.β-elemene has great anti-tumor collaborative functions.

摘要： The expression of paired immunoglobin-like receptors A (PIR-A) and B (PIR-B) and their relationship with tolerogenic dendritic cells (T-DC) in mice were investigated. The mouse DCs line, DC2.4 cells were cultured with the recombinant murine interleukin-10 (IL-10) and recombinant human transforming growth factor β1 (TGF-β1) respectively to develop the T-DC and stimulated with lipopolysaccharide (LPS) for 48 h to induce the mature dendritic cells (LPS-DC). Special small interfering RNAs (siRNA) molecule for PIR-B was chemically synthesized and transfected into DC2.4 cells (Si-DC) by lip2000. The expression of PIRs on DC2.4 cells were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), flow cytometry (FCM) and Western blot. Realtime reverse transcriptase-polymerase chain reaction (Realtime-PCR) was applied for measurement of PIR-A and CD80, CD86, MHC-Ⅱ mRNA expression. The allogeneic stimulating capacity of DCs was measured by mixed lymphocyte reaction (MLR) using 3H-thymidine incorporation test. The concentration of IFN-γ in supernatants of MLR from distinct groups was analyzed by ELISA. The results showed that PIR positive rate was (28.65±8.12)% examined by FCM on DC2.4 cells. PIR positive rate was increased dramatically to (54.21±6.34)%, (58.78±4.70)%,(48.24±6.75)% respectively for IL-10, TGF-β1 and LPS induction (P＜0.01), but there was no significantly different among the three groups (P＞0.01). The semi-quantitative RT-PCR and Western blot revealed that IL-10 and TGF-β1 induced the higher PIR-B level and lower PIR-A level. On the contrary, the LPS down-regulated the PIR-B expression and up-regulated the PIR-A expression.Realtime PCR examination demonstrated that PIR-A and co-stimulating molecules such as CD80,CD86 and MHC-Ⅱ were increased significantly after stimulation with LPS. Compared with the DC2.4 cells and the LPS-DC, the T-DCs inhibited alloactived T cell proliferation and down-regulated the IFN-γ secretion in MLR supernatant. Si-DC promoted the T cell proliferation (P＜0.01) and enhanced the IFN-γ secretion (P＜0.01). It was concluded that up-regulating the PIR-B and down-regulating the PIR-A expression were the general feature of phenotype and constructed the new targets for dendritic cells to acquire immune tolerance in mice. Overexpression of PIR-B can inhibit the up-regulation of the PIR-A, CD80, CD86 and MHC- Ⅱ expression, which might be the molecular mechanism for the T-DC.