Synthetic TGF-β Signaling Agonist-Treated Dendritic Cells Induce Tolerogenicity and Antirheumatic Effects.

The newly synthesized compound TGF-β signaling agonist (T74) is a small molecule associated with the TGF-β receptor signaling pathway. Tolerogenic dendritic cells (tDCs) have been used to examine immunosuppressive and anti-inflammatory effects in multiple autoimmune disease models. The aim of this study was to investigate whether treatment of DCs with T74 has an antirheumatic effect in a mouse model of collagen-induced arthritis (CIA).

TNF-α Induces Mitophagy in Rheumatoid Arthritis Synovial Fibroblasts, and Mitophagy Inhibition Alleviates Synovitis in Collagen Antibody-Induced Arthritis.

Mitophagy is a selective form of autophagy that removes damaged mitochondria. Increasing evidence indicates that dysregulated mitophagy is implicated in numerous autoimmune diseases, but the role of mitophagy in rheumatoid arthritis (RA) has not yet been reported. The aim of the present study was to determine the roles of mitophagy in patient-derived RA synovial fibroblasts (RASFs) and in the collagen antibody-induced arthritis mouse model.

TGF-β/IL-7 Chimeric Switch Receptor-Expressing CAR-T Cells Inhibit Recurrence of CD19-Positive B Cell Lymphoma.

Chimeric antigen receptor (CAR)-T cells are effective in the treatment of hematologic malignancies but have shown limited efficacy against solid tumors. Here, we demonstrated an approach to inhibit recurrence of B cell lymphoma by co-expressing both a human anti-CD19-specific single-chain variable fragment (scFv) CAR (CD19 CAR) and a TGF-β/IL-7 chimeric switch receptor (tTRII-I7R) in T cells (CD19 CAR-tTRII-I7R-T cells). The tTRII-I7R was designed to convert immunosuppressive TGF-β signaling into immune-activating IL-7 signaling.

Functional Ambivalence of Dendritic Cells: Tolerogenicity and Immunogenicity.

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and inducers of T cell-mediated immunity. Although DCs play a central role in promoting adaptive immune responses against growing tumors, they also establish and maintain peripheral tolerance. DC activity depends on the method of induction and/or the presence of immunosuppressive agents.

The Effect of the Tumor Microenvironment and Tumor-Derived Metabolites on Dendritic Cell Function.

Dendritic cells (DCs) have a critical effect on the outcome of adaptive immune responses against growing tumors. Recent studies on the metabolism on DCs provide new insights on the functioning of these critical controllers of innate and adaptive immunity. DCs within the tumor microenvironment (TME) often exist in an inactive state, which is thought to limit the adaptive immune response elicited by the growing tumor.

Sequential treatment with aT19 cells generates memory CAR-T cells and prolongs the lifespan of Raji-B-NDG mice.

Treatment with chimeric antigen receptor (CAR)-modified T cells targeting CD19 has proved successful in patients with relapsed/refractory B cell malignancies. However, long-term follow-up indicates that remission in a substantial proportion of patients is not sustainable. Most patients that experience recurrence have tumors and lost the CAR-T cells.

Pdlim4 is essential for CCR7-JNK-mediated dendritic cell migration and F-actin-related dendrite formation.

Dendritic cells (DCs) are the most potent professional antigen (Ag)-presenting cells and inducers of T cell-mediated immunity. A previous microarray analysis identified PDZ and LIM domain protein 4 (Pdlim4) as a candidate marker for DC maturation. The aim of this study was to investigate whether Pdlim4 influences DC migration and maturation.

Rsad2 is necessary for mouse dendritic cell maturation via the IRF7-mediated signaling pathway.

Dendritic cells (DCs) are the most potent professional antigen presenting cells and inducers of T cell-mediated immunity. However, few specific markers of mature DCs (mDC) have been reported. A previous microarray analysis revealed expression of mDC-specific genes and identified Rsad2 (radical S-adenosyl methionine domain containing 2) as a candidate specific marker for DC maturation.

Dendritic Cell-Based Immunotherapy for Solid Tumors.

As a treatment for solid tumors, dendritic cell (DC)-based immunotherapy has not been as effective as expected. Here, we review the reasons underlying the limitations of DC-based immunotherapy for solid tumors and ask what can be done to improve immune cell-based cancer therapies. Several reports show that, rather than a lack of immune induction, the limited efficacy of DC-based immunotherapy in cases of renal cell carcinoma (RCC) likely results from inhibition of immune responses by tumor-secreted TGF-β and an increase in the number of regulatory T (Treg) cells in and around the solid tumor.

Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage Polarization.

Background: Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases.

Methods: We generated tDCs by treating bone marrow-derived dendritic cells with tumor necrosis factor-α and cardiac lysate from MI mice.

Dendritic Cell Immunotherapy Combined with Cytokine-Induced Killer Cells Effectively Suppresses Established Hepatocellular Carcinomas in Mice.

Background: The response of hepatocellular carcinoma (HCC) to immunotherapy is often disappointing and new strategies are clearly needed. The aim of the present study was to investigate whether cytokine-induced killer (CIK) cells combined with a dendritic cell vaccination enhanced cytotoxicity against hepatocarcinoma tumor cells in an in vivo animal model.

Methods: CIKs and DCs were prepared from C3H/HeJ mice by conventional methods, the dendritic cell (DC) pulsed with a MH134 cell lysate, DC or CIK alone were used as controls.

Rosiglitazone-mediated dendritic cells ameliorate collagen-induced arthritis in mice.

Rosiglitazone is a selective ligand for peroxisome proliferator-activated receptor-gamma (PPAR-γ), which serves diverse biological functions. A number of autoimmune disease models have been used to examine the anti-inflammatory and immunosuppressive effects of tolerogenic dendritic cells (tDCs). The aim of the present study was to investigate whether rosiglitazone-mediated DC (Rosi-DC) therapy suppressed arthritis in a collagen-induced arthritis (CIA) mouse model.

Tolerogenic dendritic cells show gene expression profiles that are different from those of immunogenic dendritic cells in DBA/1 mice.

Tolerogenic dendritic cells (tDCs) play an important role in inducing peripheral tolerance; however, few tDC-specific markers have been identified. The aims of this study were to examine whether tDCs show a different gene expression profile from that of immunogenic DCs and identify specific gene markers of each cell type, in DBA/1 mice. tDCs were generated by treating immature DCs (imDCs) with TNF-α and type II collagen.

Myosin-primed tolerogenic dendritic cells ameliorate experimental autoimmune myocarditis.

Aims: Autoimmunity plays an important role in the pathogenesis of viral myocarditis and giant cell myocarditis. Experimental autoimmune myocarditis (EAM) is a mouse model of myocarditis that is induced by cardiac myosin. Tolerogenic dendritic cells (tDCs) are used as anti-inflammatory and immunosuppressive targets in a number of autoimmune disease models, but their effect on EAM has not been addressed.

Electronic nose based on multipatterns of ZnO nanorods on a quartz resonator with remote electrodes.

An electrodeless monolithic multichannel quartz crystal microbalance (MQCM) sensor was developed via the direct growth of ZnO nanorod patterns of various sizes onto an electrodeless quartz crystal plate. The patterned ZnO nanorods acted as independent resonators with different frequencies upon exposure to an electric field. The added mass of ZnO nanostructures was found to significantly enhance the quality factor (QF) of the resonator in electrodeless QCM configuration.

Development of galvanostatic Fourier transform electrochemical impedance spectroscopy.

Here, we report development of the galvanostatic Fourier transform electrochemical impedance spectroscopy (FTEIS), which monitors impedance of electrochemical reactions activated by current steps. We first derive relevant relations for potential change upon application of a step current, obtain impedances theoretically from the relations by simulation, and verify them with experimental results. The validity of the galvanostatic FTEIS technique is demonstrated by measuring impedances of a semiconductive silicon wafer using the conventional frequency response analysis (FRA), the potentiostatic FTEIS, and the galvanostatic FTEIS methods, and the results are in excellent agreement with each other.

Phase I/II study of immunotherapy using tumor antigen-pulsed dendritic cells in patients with hepatocellular carcinoma.

Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days.

Quartz resonator for simultaneously measuring changes in the mass and electrical resistance of a polyaniline film.

A novel quartz resonator was developed to measure, simultaneously, changes in the mass and electrical resistance of a polyaniline film during the absorption of water vapor. Interdigitated gold electrodes were vacuum-deposited on the sensing surfaces of the quartz crystals, and polyaniline films were drop-cast on the electrodes used to measure the changes in the electrical resistance. Two symmetric semicircular gold electrodes were deposited on the bottom surface of the quartz crystal.

Photodynamic therapy-mediated DC immunotherapy is highly effective for the inhibition of established solid tumors.

Dendritic cell (DC)-mediated immunotherapy has not been as effective as expected for most solid tumors. This study demonstrates immune responses against solid tumors mediated by DCs charged with photodynamic therapy (PDT)-induced tumor lysates, which contain the heat shock protein (HSP) 70. PDT tumor lysate-pulsed DC (PDT-DC) inhibited the growth of mammary EMT6 tumors to a greater extent than freeze/thawed tumor lysate-pulsed DC (FT-DC) or PDT tumor lysates.

Phase transitions between the rotator phases of paraffin investigated using silicon microcantilevers.

Nanogram amounts of paraffin were coated onto a silicon cantilever, and the resonance frequency and deflection of the cantilever were measured as a function of temperature. Changes in the cantilever resonance frequency were used to determine the temperatures at which phase transitions between the rotator phases of tricosane, tetracosane, and pentacosane occurred. The phase transition measured using the cantilever was found to be more apparent than that obtained using conventional methods.

A visible light-induced photocatalytic silver enhancement reaction for gravimetric biosensors.

We have developed a novel microgravimetric immunosensor using a WO(3) nanoparticle-modified immunoassay and a silver enhancement reaction. When the nanoparticles in silver ion solution (i.e.

Gravimetric analysis of the adsorption and desorption of CO2 on amine-functionalized mesoporous silica mounted on a microcantilever array.

The kinetics of CO(2) adsorption and desorption over amine-functionalized mesoporous silica were investigated using silicon microcantilever arrays. Three types of mesoporous silica with different pore sizes were synthesized and functionalized with a variety of amine molecules. After depositing the silica sorbents onto the free end of each cantilever in an array, mass changes due to the adsorption and desorption of CO(2) were determined in situ with picogram sensitivity by measuring variations in the cantilever frequencies.

Photocatalytic silver enhancement reaction for gravimetric immunosensors.

A novel microgravimetric immunosensor has been developed using TiO(2) nanoparticle-modified immunoassay and silver enhancement reaction. An antibody-conjugated TiO(2) nanoparticle is bound to the AFP antigen immobilized on a quartz resonator. When the nanoparticles are exposed to UV light in a silver nitrate solution, the photocatalytic reduction of silver ions results in the formation of metallic silver onto the nanoparticles and induces a decrease in the resonance frequency.

Microthermogravimetry of a single microcapsule using silicon microresonators.

A chlorobenzene-containing polyurethane microcapsule was placed on the free end of a silicon cantilever, and the temperature dependence of the resonance frequency was measured. As the cantilever was heated, the resonance frequency showed steplike increases at 109 and 270 degrees C that were due to the rupture of the capsule and the thermal degradation of the polyurethane shell, respectively. The frequency changes due to the rupture of a single capsule measured by the cantilever were much sharper than the transitions measured by conventional thermogravimetric analysis (TGA), which measures the average mass change of a collection of capsules characterized by a large size distribution.