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Plasmacytoid dendritic cells (pDCs) are a unique subset of dendritic cells that can rapidly produce large amounts of type Ⅰ interferon after activation. They are critical in antiviral immunity and involved in the initiation and development of many autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease characterized by immune dysregulation, vasculopathy and progressive fibrosis of the skin and internal organs. Recent studies have found that pDCs are involved in the pathogenesis of SSc. Inhibiting the function of pDCs can effectively prevent inflammation and fibrosis in SSc, highlighting the role of pDCs in the pathogenesis of SSc. Therefore, an in-depth understanding of pDCs and their role in the pathogenesis of SSc is important for the development of pDCs and their mediators as therapeutic targets for SSc.
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Objective@#To investigate the feasibility of myeloid and plasmacytoid dendritic cell combined vaccines loaded with heat-treated Lewis lung cancer cell lysates for treatment of lung cancer in mice.@*Methods@#Bone marrow cells were induced by the recombinant mouse fms-like tyrosine kinase receptor 3 ligand (rmFlt3-L) in vitro, myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) were separated by magnetic beads. The mDC, pDC, and mDC∶pDC=1∶1 were stimulated with heat-treated Lewis lung cancer cell lysates, respectively. The effects of each group on stimulating of lymphocyte proliferation and inducing of T cell to kill tumor cells in vitro were compared. The alternations of the immunophenotypes of CD80, CD86, CD40 and major histocompatibility complex Ⅱ (MHC-Ⅱ) were detected by flow cytometry. The secretion of cytokines including interlukin-12 (IL-12), interlukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA).@*Results@#The lymphocyte proliferation in mice stimulated with mDC+ pDC group loaded with heat-treated Lewis lung cancer cell lysates was 10.80±0.66, significantly higher than 8.63±0.65 of mDC group and 7.10±0.46 pDC group under the same culture conditions, respectively (P<0.05). When the ratio of effector cells: target cells (E∶T) was 10∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 31.68%±2.93%, significantly higher than 17.44%±0.97% of mDC group and 10.29%±1.33% of pDC group, respectively (P<0.05). When the ratio of E∶T was 20∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 54.77%±3.28%, significantly higher than 35.25%±1.51% of mDC group and 15.52%±0.73% of pDC group, respectively (P<0.05). When the ratio of E∶T was 40∶1, the killing rate of the mDC+ pDC group loaded with heat-treated tumor cell lysate was 73.01%±0.91%, significantly higher than 51.36%±0.58% of mDC group and 22.65%±1.28% of pDC group, respectively (P<0.05). With the rate of E∶T increased, the killing rate also increased. The mean fluorescence intensities of surface molecules including CD80, CD86, CD40 and MHC-Ⅱ of mDC: pDC=1 group pulsed with heat-treated Lewis lung cancer cell lysates were higher than those of mDC group and pDC group. The IL-6 cytokine concentrations of mDC+ pDC group, mDC group and pDC group loaded with heat-treated Lewis lung cancer cell lysates were (586.67±52.52) pg/ml, (323.33±67.14) pg/ml and (166.67±16.07) pg/ml, respectively. The concentrations of IL-12 in each group were (2 568.75±119.24) pg/ml, (2 156.25±120.55) pg/ml and (672.92±31.46) pg/ml, respectively. The concentrations of TNF-α in each group were (789.33±48.08) pg/ml, (584.89±116.49) pg/ml and (291.56±40.73) pg/ml, respectively. The concentrations of IL-6, IL-12 and TNF-α secreted by mDC+ pDC group were much higher than those of mDC group and pDC group under the same culture conditions (P<0.05).@*Conclusions@#The mDCs and pDCs combined vaccines pulsed with heat-treated Lewis lung cancer cell lysates have synergistic effects on inducing of T lymphocyte proliferation and killing tumor cells in vitro. This synergistic anti-tumor effect is related with up-regulation of co-stimulatory molecules and increased secretion of cytokines.
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Objective@#To investigate the correlation between the frequency and function of early plasmacytoid dendritic cells (pDC) and the treatment response in patients with HBeAg-positive chronic hepatitis B receiving entecavir (ETV).@*Methods@#Patients with HBeAg-positive chronic hepatitis B were enrolled. Antiviral therapy with ETV, serum serological markerso hepatitis B virs (HBV) infection and liver function (HBV DNA load, HBsAg/anti-HBs, HBeAg and anti-HBe levels, and ALT levels) were monitored every three months before and during treatment; the efficacy of ETV was assessed by changes in the level of HBV DNA. Peripheral venous blood was collected before treatment, at 12 weeks and 24 weeks, respectively. Flow cytometry was used to detect the frequency of peripheral blood pDC and the surface co-stimulatory molecule CD86. The baseline and early treatment (12 weeks and 24 weeks) pDC frequency and functional changes were analyzed.@*Results@#Of the 100 patients with chronic hepatitis B, 45 patients received ETV treatment and 48 weeks of follow-up. Within 48 weeks of ETV treatment, HBsAg levels decreased by 0.53±0.78 log IU/mL; HBeAg decreased by 816.61S/CO, and HBeAg seroconversion occurred in 4 cases; HBV DNA content decreased by 6.04±1.12 log IU/mL, in 33 cases (73%) the HBV DNA became undetectable, in 43 cases ALT kept normal continuously for more than 3 months. In the early stage of ETV treatment, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes. In ETV-treated HBV DNA responders, pDC% increased significantly, CD86+ pDC%, CD86MFI and CD86ABC showed no significant changes; HBV DNA non-responders had a significant increase in pDC%, but CD86+ pDC% decreased significantly, and CD86MFI and CD86ABC showed no significant changes. The decrease in HBsAg and HBeAg levels in ETV treated patients was not significantly associated with early pDC%, CD86+ pDC%, CD86MFI and CD86ABC changes.@*Conclusions@#ETV treatment can directly inhibit the replication of HBV DNA, but does not enhance the function of immune cells.
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Objective To investigate the clinical features, diagnosis, treatment and prognosis of myelodysplastic syndromes (MDS) with mature plasmacytoid dendritic cells (PDC) proliferation. Methods The clinical data of one case of MDS with excess blasts (EB)﹣1 with mature PDC proliferation in Air Force Medical Center was retrospectively analyzed, and the literature was reviewed. Results The patient′s physical examination revealed anemia and thrombocytopenia. Bone marrow smears showed 0.064 of myeloblasts and 0.152 of dendritic cells. Immunophenotyping showed two groups of abnormal proliferation cells, namely, myeloblasts and mature PDC. Decitabine treatment was given, and the red blood cells and platelets were infused intermittently. The condition of patient was basically stable. Conclusions MDS with mature PDC proliferation is extremely rare. No special clinical manifestations are found, and the diagnosis is based on bone marrow cytology and immunophenotyping. There is no standard regimen for treatment of MDS with mature PDC proliferation, and the prognosis depends on the progression of MDS.
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The study is aimed to evaluate the anti-HIV-1 effect of chloroquine in combination with antihuman immunodeficiency virus (HIV) drugs, and inhibition of plasmacytoid dendritic cells (pDC) activation and type I interferon (IFN-I) production by Toll-like receptor 7 (TLR7) agonist stimulation. We investigated the anti-HIV-1ⅢB, HIV-1KM018 activity of chloroquine and chloroquine combined with rategrivir (RAL), enfuvirtide (T-20), indinavir (IDV) and efavirenz (EFV) in vitro by luciferase activity assay system and ELISA method for p24 antigen. We measured the effect of chloroquine on the activation of pDC in combination with RAL and IDV, respectively. Quantitative PCR was used to evaluate the activity of chloroquine in combination with RAL and IDV in the upregulation of interferon (IFN)-α and IFN-β. Chloroquine showed less cytotoxicity to C8166, TZM-bl and PBMC cells, and the 50% cytotoxic concentration values were 85.02 ±0.28, 73.67 ±5.10 and 91.84 ±4.10 μmol·L-1, respectively. The anti-HIV-1ⅢB activity of chloroquine combination with RAL, T-20, IDV and EFV were moderate in synergy, strong in synergy, additive and moderate antagonism, respectively. The anti-HIV-1KM018 activity of chloroquine in combination with RAL, IDV were moderate synergy, minor synergy. There was no significant difference between the chloroquine monotherapy and chloroquine combined with RAL, IDV in the down-regulation of pDC activation and IFN-α, IFN-β expression levels. We have found that chloroquine combined with different anti-HIV drugs represent different degrees of synergism, antagonism or additive anti-HIV-1 effect. Chloroquine in combination with RAL and IDV did not have influence on the inhibitory effect of chloroquine on pDC activation and type I interferon secretion induced by TLR7 agonist. The results suggest that chloroquine may be used to enhance the therapeutic activities of anti-HIV medicines.
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Aryl hydrocarbon receptor (AhR) regulates both innate and adaptive immune responses by sensing a variety of small synthetic and natural chemicals, which act as its ligands. AhR, which is expressed in dendritic cells (DCs), regulates the differentiation of DCs. However, effects of AhR on the differentiation of DCs are variable due to the heterogeneity of DCs in cell surface marker expression, anatomical location, and functional responses. The plasmacytoid DCs (pDCs), one of DC subsets, not only induce innate as well as adaptive immune responses by secreting type I interferons and pro-inflammatory cytokines, but also induce IL-10 producing regulatory T cell or anergy or deletion of antigen-specific T cells. We showed here that AhR ligands indoxyl 3-sulfate (I3S) and indole-3-carbinol (I3C) inhibited the development of pDCs derived from bone marrow (BM) precursors induced by FMS-like tyrosine kinase 3 ligand (Flt3L). I3S and I3C downregulated the expression of signal transducer and activator of transcription 3 (STAT3) and E2-2 (Tcf4). In mice orally treated with I3S and I3C, oral tolerance to dinitrofluorobenzene was impaired and the proportion of CD11c⁺B220⁺ cells in mesenteric lymph nodes was reduced. These data demonstrate that AhR negatively regulates the development of pDCs from BM precursors induced by Flt3L, probably via repressing the expression of STAT3.
Subject(s)
Animals , Mice , Bone Marrow , Cell Differentiation , Cytokines , Dendritic Cells , Dinitrofluorobenzene , fms-Like Tyrosine Kinase 3 , Immune Tolerance , Interferon Type I , Interleukin-10 , Ligands , Lymph Nodes , Population Characteristics , Receptors, Aryl Hydrocarbon , STAT3 Transcription Factor , T-Lymphocytes , Vascular Endothelial Growth Factor Receptor-1ABSTRACT
Objective:To investigate the immunomodulation of CCK8 on the Coxsackievirus B ( CVB )-attacked human peripheral blood plasmacytoid dendritic cells(pDC). Methods:Peripheral blood mononuclear cells of healthy volunteers were separated by Ficoll-Hypaque gradient density centrifugation. The pDC was separated and divided into five groups,which were the control group, CVB attacked group,the group of CCK8 treated after CVB attack,the group of PGE2 treated after CVB attack and the group of CCK8+PGE2 treated after CVB attack. 100-time TCID50 of CVB was applied for the attack on pDC. Real-time PCR and Immunofluorescence technique were employed to detect the expression of CCK1R/CCK2R mRNA and protein. Then,the expression levels of costimulatory molecules such as CD80,CD86,HLA-DR ligand,and the chemokine receptor CCR7 were evaluated by Flow Cytometry Analysis. The supernatants of pDCs were collected, and the content of IFN-α was determined by Enzyme-linked Immunosorbent Assay. Results:CCK1R and CCK2R were co-expressed in human peripheral blood pDC,and both were significantly upregulated after CVB attack in vitro. Expression of CD80,CD86,HLA-DR and IFN-α were decreased in the CVB+CCK8 group compared with the CVB group,which suggested that CCK8 may reduce the CVB activation of pDC. Whereas expression of CD80,CD86,HLA-DR,CCR7 and IFN-α were increased in the CVB+PGE2 group compared with the CVB group,which suggested that PGE2 may increase the CVB activation of pDC in vitro. Conclusion:CCK8 repressed the CVB-attacked pDC,while PGE2 activated the CVB-attacked pDC.
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Objective@#To investigate the differences in function of plasmacytoid dendritic cells (pDC) and CD4+ T helper cells (CD4+ Th cells) between acute hepatitis B (AHB) and chronic hepatitis B (CHB).@*Methods@#In this study, patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of pDC, CD86+ pDC, CD4+ T cells and their subsets, surface functional molecules were detected respectively among patients with chronic HBV infection in IA phase, patients with AHB, those recovered from AHB. Meanwhile, their correlations with ALT, HBV DNA and HBV markers were analyzed.@*Results@#The ALT level in AHB was significantly higher than that in IA, and inflammation was more obvious in AHB. Between IA and AHB, CD86+ pDC frequency and the mean fluorescence intensity of functional molecule CD86 (CD86MFI) were higher in IA than those in AHB, but the frequency of CD4+ T cells in AHB was higher than that in IA. For patients who got over AHB, the frequency of CD86+ pDC increased; Th1 were on the rise, while the frequencies of CD4+ T and Th2 decreased after the recovery of AHB, and Th2 / Th1 ratio decreased..In AHB, HBVDNA loads were positively correlated with ALT levels and Th2 frequencies.@*Conclusions@#In CHB immune active phase, CD86+ pDC with stimulating function played an important role, but the cellular immune response of CD4+ T cells decreased. In AHB inflammatory stage, CD4+ T cells played a strong cellular immune response, which result ed in viral clearance. Th2 cells regulation of CD4+ T cells played a dominant role, which was involved in the inflammatory response, and the cytotoxic role of Th1 cells during the recovery period was dominant, playing a strong cellular immune response, then the virus were completely eliminated.
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Objective:To investigate the functional status of dendritic cells(DCs)in oral leukoplakia(OLK)tissues.Methods:The expression of DC-specific markers CD1 a,CD209,CD1 23 and CD83 in 20 cases of OLK with abnormal dysplasia,1 0 with simple dys-plasia and 1 0 of normal oral mucosa tissues was examined by immunohistochemistry.Results:CD1 a and CD209 positive DCs were found in all cases.More CD1 a positive Langehans cells(LCs)in lamina propria were found in OLK with abnormal dysplasia than in normal o-ral mucosa and OLK with simple dysplasia(P <0.01 ).A great mount of CD209 positive stromal DCs were recruited in OLK.There was no CD83 positive and CD1 23 positive cell in normal oral mucosa,however,CD83 positive mature DCs and CD1 23 positive plasmacytoid DCs(PDCs)were observed in OLK(P <0.01 ).Conclusion:OLK is characterized by the recruitment of different subsets of DCs,the different DC subsets may play an important role in the development of OLK.
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Objective To investigate the alterations of plasmacytoid dendritic cells ( pDC) in pa-tients with primary Sj?gren′s syndrome ( pSS) and their significance.Methods Peripheral blood samples were collected from 39 patients with pSS and 15 healthy subjects.The percentages of pDC ( Lin-CD123+HLA-DR+) in peripheral blood samples were analyzed by flow cytometry.The levels of IFN-α, TNF-αand IL-6 in serum samples were detected by ELISA.Results The percentages of pDC in patients with pSS were lower than those in healthy subjects (P<0.05).Higher levels of pDC were detected in patients positive for anti-Sj?gren syndrome antigen A ( anti-SSA) antibody as compared with those in patients negative for anti-SSA antibody.The levels of TNF-αand IL-6 in serum samples from patients with pSS were higher than those in healthy subjects.Conclusion Patients with pSS showed decreased percentages of pDC population, but increased levels of TNF-αand IL-6.The changes of pDC population, TNF-αand IL-6 in peripheral blood might play active roles in the pathogenesis of pSS.
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Objective To provide new information for treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN).Methods Through one case report and literature review of 48 BPDCN cases were reviewed retrospectively.The clinical characteristics,treatment choices and prognosis were analyzed.Results BPDCN patients were mainly elderly males,mostly presented as skin rash and bone marrow infiltration.Immunophenotype was characteristically expressed as CD4,CD56 and CD123.Lymphoid-like regimens could induce higher response rate,lower relapse rate and longer overall survival compared with myeloid-like regimens.Allogeneic hematopoietic stem cell transplantation may provide long-term survival.At the onset of the disease,The counts of white blood cells (WBC) and blood platelet (Plt) may be correlated with inferior overall survival.Conclusions BPDCN is a disease with distinct clinical characteristics and immunophenotype.Lymphoid-like regimen may be the better treatment of choice,while allogeneic hematopoietic stem cell transplantation should be taken into account in the first complete remission for longterm survival.
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Objective To investigate the expression and distribution of plasmacytoid dendritic cells(pDC) in peripheral blood and renal tissues in children with Henoch-SchSnlein purpura(HSP),and explore the role of pDCs in the pathogenesis of Henoch-Schtnlein purpura nephritis(HSPN).Methods Among the 40 children with HSP,28 cases were in the active phase(renal biopsy performed in 8 cases of them) and the other 12 in remission phase.Peripheral blood mononuclear cells were isolated,and the expression of pDC was detected by flow cytometry.The normal control group was established (n =15).Total RNA of peripheral blood was extracted and transcripted into cDNA.Sybr green dye based real-time quantitative PCR method was used to compare the expression(indicated as 2-△Ct value) of CXC motif chemokine 10 (CXCL10),CC chemokine ligand 5 (CCL5),chemokine CXC subfamily receptor 3 (CXCR3),CC chemokine receptor 5 (CCR5) in children with HSP and those in the controls.Immunohistochemistry labeling technique was used to detect the distribution of pDC in renal tissues from renal biopsy,and the normal controls were established (n =3).Results The expression percentage of pDC in peripheral blood in active phase was 0.051 ± 0.039,significantly lower than those in remission phase (0.181 ± 0.082) and the normal controls (0.166 ± 0.079) (P ＜ 0.000 1).Chemokines genes CXCL10 and CCL5 were overexpressed in peripheral blood ceils of acute phase HSP children,but chemokine receptors CXCR3,CCR5 were lowly expressed compared with normal controls.There was almost no expression of pDC in the normal control renal tissues,while pDC was infiltrated in glomeruli of HSPN children.Conclusions The number of pDC and chemokines' expression in peripheral blood is abnormal,and the pathogenesis of nephritis may be involved with the pDC in peripheral blood to migrate to the renal tissues.
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Objective To investigate the changes of plasmacytoid dendritic cells (pDC) in peripheral blood of patients with systemic lupus erythematosus(SLE) and its roles in the pathogenesis of SLE.Methods The level of pDC and the expressions of CD32,CD40,CD86,CD62L and CXCR4 were analyzed by flow cytometry.The concentrations of IFN-α in serum were detected by ELISA assay.Results The levels of circulating pDC were significantly decreased in SLE patients compared with healthy controls.Moreover,the pDC levels in active SLE patients were lower than those in inactive SLE patients,and compared with the primary group,the pDC levels were increased in the treatment group.The levels of pDC showed a significant decrease in SLE patients with arthritis,proteinuria or leucopenia in comparison with patients without those manifestations,showing a negative correlation with proteinuria.The expressions of cell surface molecules including CD32,CD86,CD62L and CXCR4 on pDCs were significantly increased in SLE patients compared with healthy controls,and the levels of pDC were negatively correlated with the expressions of CD32 and CXCR4 in patients with SLE.The concentrations of IFN-α in serum of patients with SLE were significantly higher than those in healthy controls,and the levels of pDC were positively correlated with the concentrations of IFN-α in patients with SLE.Conclusion The level of circulating pDC in patients with SLE was remarkably reduced,but the expressions of molecules involved in cell activation and migration were upregulated,accompanied by enhanced IFN-α production,which might promote the onset and progression of SLE.
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La psoriasis es una enfermedad inflamatoria crónica de la piel mediada por células T que afecta a individuos con predisposición genética y presenta varios subtipos clínicos. Se caracteriza por la presencia de placas eritematosas bien definidas, escamosas y de bordes irregulares, que afectan fundamentalmente las regiones de los codos, las rodillas, el cuero cabelludo y el tronco. El alelo HLA-Cw6 del sistema principal de histocompatibilidad está relacionado con la presencia y severidad de la enfermedad. Desde el punto de vista fisiopatogénico, la psoriasis es una enfermedad inmune de tipo Th1, en la que es fundamental el eje IL-23/Th17. Las células Th17 producen las citocinas proinflamatorias (IL-17A, IL-17F, IL-22 e IL-26) que activan los queratinocitos y causan hiperproliferación y mayor producción de citocinas proinflamatorias y péptidos antimicrobianos, los que a su vez reclutan y activan otras células inmunes de la piel inflamada. Se produce así una amplificación de la respuesta inflamatoria que conduce a las manifestaciones clínicas de la enfermedad. El tratamiento de la psoriasis incluye agentes antiinflamatorios tópicos, fototerapia, inmunosupresores sistémicos y agentes biológicos, entre los que se encuentran las proteínas de fusión, los inhibidores del factor de necrosis tumoral alfa y los inhibidores de las interleucinas 12 y 23
Psoriasis is a T cell-mediated chronic inflammatory disease of the skin. It affects genetically predisposed individuals and presents several subtypes. It is characterized by the presence of well-defined erythematous, scaly, irregular border plaque or lesions, affecting mainly the elbows, knees, scalp, and trunk. The HLA-Cw6 allele of major histocompatibility system is related to the presence and severity of this disease. From the physiopathogenic viewpoint, psoriasis is a Th1-type immune disease in which the axle IL-23/Th17 is fundamental. Th17 cells produce proinflammatory cytokines (IL-17A, IL-17F, IL-22 and IL-26) which activate keratinocytes and cause hyperproliferation and increased production of proinflammatory cytokines and antimicrobial peptides. The latter, in turn, recruit and activate other immune cells of swollen skin. There is thus an amplification of the inflammatory response that leads to clinical manifestations of this disease. The treatment of psoriasis includes topical antiinflammatory agents, phototherapy and systemic immunosuppressive biological agents, including those which are fusion proteins, inhibitors of alpha tumor factor necrosis, and interleukin inhibitors 12 and 23
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Humans , Male , Female , Psoriasis/complications , Psoriasis/epidemiology , Psoriasis/immunology , Sickness Impact ProfileABSTRACT
El tumor blástico a células dendríticas plasmacitoides (TBCDP) es una malignidad hematopoyética rara, altamente agresiva, derivada de las células dendríticas plasmocitoides; se caracteriza por su alta incidencia de compromiso cutáneo, que a menudo termina en una fase leucémica de mal pronóstico. La primera manifestación de la enfermedad pueden ser placas y tumores solitarios o múltiples, de manera que la biopsia cutánea es crucial para el diagnóstico. En la histopatología se observa un infiltrado difuso, monomorfo, no epidermotrópico de células de tamaño mediano con núcleos redondos, cromatina finamente dispersa, CD4 + CD56 + CD 123 +. Presentamos el caso de una paciente de sexo femenino de 48 años con un tumor plasmocitoide de células dendríticas. Al examen dermatológico se observaron lesiones cutáneas en cara externa de la pierna izquierda y mama derecha, acompañados de adenopatías inguinales palpables. No se halló compromiso de médula ósea y el hemograma fue normal. La paciente fue tratada con metotrexato, L-asparaginasa y dexametasona con buena respuesta clínica. El trasplante alogénico fue propuesto después del tercer ciclo.
Blastic neoplasm of plasmacytoid dendritic cells (BNPDC) is a rare hematopoietic malignancy, highlyaggressive, derived from plasmacytoid dendritic cells, and is characterized by a high incidence of cutaneousinvolvement, common leukemic dissemination and poor prognosis. Solitary or multiple skin plaques andtumors are often the first clinical manifestations of the disease; thus, cutaneous biopsies are crucial tocorrectly classify the patients. Histopathologic features are characterized by diffuse, monomorphous, nonepidermotropic infiltrates of medium-sized cells with round nuclei, finely dispersed chromatin CD4+CD56+ CD123+. We describe a 48-year-old woman who presented BNPDC. Clinically, two isolated bruiselikelesions arising on her left leg and right breast were detected, with palpable inguinal lymph nodes.Peripheral blood smear was normal, and the bone marrow was not involved. The patient was treatedwith methotrexate, L- asparaginase and dexametasone before entering in an allogenic bone marrowtransplantation program.
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Humans , Adult , Female , Lymphoma/pathology , Lymphoma/drug therapy , Lymphoma/therapy , Dendritic Cells/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/therapyABSTRACT
Objective To explore the mechanism of immunomodulatory activity of triptolide on healthy volunteers peripheral blood mononuclear cells (PBMC)-derived plasmacytoid dendritic cells (pDCs). Methods Healthy volunteers-derived pDCs were sorted by flow cytometry, then incubated with triptolide (0, 5, 10, 30 μg/L). After 24 hours, we detected the concentration of IFN-α, IL-6, TNF-α using ELISA. After 5 days, the cultrural cells were collected and analyzed by flow cytometry, light microscope and electron microscope scanning. Results Triptolide-treated pDCs secreted lower level of IFN-α,IL-6 ,TNF-α, triptolide could inhibit pDCs differentiation to DCs which displayed more immature morphology and immunophenotypes than untreated-pDCs. Conclusion Triptolide could decrease the immune function of pDCs, inhibit differentiation and maturation of pDCs.
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BACKGROUND: CD4+Fop3+ regulatory T cells (Tregs) are needed to maintain peripheral tolerance, but their role in the development of autoimmune arthritis is still debated. The present study was undertaken to investigate the mechanism by which Tregs influence autoimmune arthritis, using a mouse model entitled K/BxN. METHODS: We generated Treg-deficient K/BxNsf mice by congenically crossing K/BxN mice with Foxp3 mutant scurfy mice. The arthritic symptoms of the mice were clinically and histopathologically examined. The proportions and activation of CD4+ T cells and/or dendritic cells were assessed in the spleens, draining lymph nodes and synovial tissue of these mice. RESULTS: K/BxNsf mice exhibited earlier onset and more aggressive progression of arthritis than their K/BxN littermates. In particular, bone destruction associated with the influx of numerous RANKL+ cells into synovia was very prominent. They also contained more memory phenotype CD4+ T cells, more Th1 and Th2 cells, and fewer Th17 cells than their control counterparts. Plasmacytoid dendritic cells expressing high levels of CD86 and CD40 were elevated in the K/BxNsf synovia. CONCLUSION: We conclude that Tregs oppose the progression of arthritis by inhibiting the development of RANKL+ cells, homeostatically proliferating CD4+ T cells, Th1, Th2 and mature plasmacytoid dendritic cells, and by inhibiting their influx into joints.
Subject(s)
Animals , Mice , Arthritis , Dendritic Cells , Joints , Lymph Nodes , Memory , Peripheral Tolerance , Phenotype , Spleen , Synovial Fluid , Synovial Membrane , T-Lymphocytes , T-Lymphocytes, Regulatory , Th17 Cells , Th2 CellsABSTRACT
BACKGROUND: CD4+Fop3+ regulatory T cells (Tregs) are needed to maintain peripheral tolerance, but their role in the development of autoimmune arthritis is still debated. The present study was undertaken to investigate the mechanism by which Tregs influence autoimmune arthritis, using a mouse model entitled K/BxN. METHODS: We generated Treg-deficient K/BxNsf mice by congenically crossing K/BxN mice with Foxp3 mutant scurfy mice. The arthritic symptoms of the mice were clinically and histopathologically examined. The proportions and activation of CD4+ T cells and/or dendritic cells were assessed in the spleens, draining lymph nodes and synovial tissue of these mice. RESULTS: K/BxNsf mice exhibited earlier onset and more aggressive progression of arthritis than their K/BxN littermates. In particular, bone destruction associated with the influx of numerous RANKL+ cells into synovia was very prominent. They also contained more memory phenotype CD4+ T cells, more Th1 and Th2 cells, and fewer Th17 cells than their control counterparts. Plasmacytoid dendritic cells expressing high levels of CD86 and CD40 were elevated in the K/BxNsf synovia. CONCLUSION: We conclude that Tregs oppose the progression of arthritis by inhibiting the development of RANKL+ cells, homeostatically proliferating CD4+ T cells, Th1, Th2 and mature plasmacytoid dendritic cells, and by inhibiting their influx into joints.
Subject(s)
Animals , Mice , Arthritis , Dendritic Cells , Joints , Lymph Nodes , Memory , Peripheral Tolerance , Phenotype , Spleen , Synovial Fluid , Synovial Membrane , T-Lymphocytes , T-Lymphocytes, Regulatory , Th17 Cells , Th2 CellsABSTRACT
Objective To explore the frequencies and phenotype of myeloid and plasmacytoid dendritic cells (mDC and pDC) in chronic HCV infection and to investigate the relationships between DC frequencies and HCV viral load and serum ALT level. Methods PBMC were isolated from chronic HCV infected patients and healthy control. Multi-color flow cytometry was used to analyze the frequencies and surface marker expression on mDC and pDC. The relationship between DC frequencies and viral load and ALT level was also calculated. Results In comparison with healthy control, frequencies of mDC and pDC in chronic HCV infection were significantly decreased (0. 37 ± 0. 19 and 0. 19 ± 0. 12 vs 0. 51 ± 0. 18 and 0. 29 ± 0.13, P＜0.05). The frequency of mDC was negatively correlated with HCV viral load (r= -0.5878, P ＜ 0. 0001 ) and serum ALT level ( r = - 0. 4628 , P = 0. 003 ). Both costimulatory markers ( HLA-DR, CD83, CD86, and CD40) and coinhibitory marker (PD-L1) expression on mDC and pDC in HCV infection were increased (P＜0.01 for costimulatory marker, P＜0.05 or F＜0.01 for coinhibitory marker). Conclusion The frequencies of mDC and pDC in chronic HCV infection were decreased, while the expression of costimulatory markers and coinhibitory marker were increased or not decreased in HCV infection. The decreased frequency of mDC was probably related to persistance of HCV infection.
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A better understanding of dendritic cell (DC) involvement in responses to haptenic drugs is needed, because it represents a possible approach to the development of an in vitro test, which could identify patients prone to drug allergies. There are two main DC subsets: plasmacytoid DC (pDC) and myeloid DC (mDC). β-lactams form hapten-carrier conjugates and may provide a suitable model to study DC behavior in drug allergy reactions. It has been demonstrated that drugs interact differently with DC in drug allergic and non-allergic patients, but there are no studies regarding these subsets. Our aim was to assess the functional changes of mDC and pDC harvested from an amoxicillin-hypersensitive 32-year-old woman who experienced a severe maculopapular exanthema as reflected in interleukin-6 (IL-6) production after stimulation with this drug and penicillin. We also aim to demonstrate, for the first time, the feasibility of this method for dendritic cell isolation followed by in vitro stimulation for studies of drug allergy physiopathology. DC were harvested using a double Percoll density gradient, which generates a basophil-depleted cell (BDC) suspension. Further, pDC were isolated by blood DC antigen 4-positive magnetic selection and gravity filtration through magnetized columns. After stimulation with amoxicillin, penicillin and positive and negative controls, IL-6 production was measured by ELISA. A positive dose-response curve for IL-6 after stimulation with amoxicillin and penicillin was observed for pDC, but not for mDC or BDC suspension. These preliminary results demonstrate the feasibility of this methodology to expand the knowledge of the effect of dendritic cell activation by drug allergens.