• BMB Reports
• /
• v.49 no.10
• /
• pp.554-559
• /
• 2016

Mycobacterium abscessus, a member of the group of non-tuberculous mycobacteria, has been identified as an emerging pulmonary pathogen in humans. However, little is known about the protective immune response of antigen-presenting cells, such as dendritic cells (DCs), which guard against M. abscessus infection. The M. abscessus gene MAB1843 encodes ᴅ-alanyl-ᴅ-alanine dipeptidase, which catalyzes the hydrolysis of ᴅ-alanyl-ᴅ-alanine dipeptide. We investigated whether MAB1843 is able to interact with DCs to enhance the effectiveness of the host's immune response. MAB1843 was found to induce DC maturation via toll-like receptor 4 and its downstream signaling pathways, such as the mitogen-activated protein kinase and nuclear factor kappa B pathways. In addition, MAB1843-treated DCs stimulated the proliferation of T cells and promoted Th1 polarization. Our results indicate that MAB1843 could potentially regulate the immune response to M. abscessus, making it important in the development of an effective vaccine against this mycobacterium.

• IMMUNE NETWORK
• /
• v.5 no.3
• /
• pp.172-178
• /
• 2005

Background: Carcinoembryonic antigen (CEA) is well-known soluble tumor marker frequently detectable in peripheral blood of carcinoma patients and considered as good target for antigen-specific immunotherapy. However, it is known that the induction of immune response to CEA is very difficult because CEA is a self-antigen expressed in fetal cells and weakly expressed in normal colorectal epithelial cells. To enhance anti-tumor immunity specific for CEA, recombinant CEA protein was modified using listeriolysin O (LLO) for endosomal lysis and trans activator of transcription (Tat) domain for transducing extracellular proteins into cytoplasm. Methods: After immunization using dendritic cells pulsed with Tat-CEA, both Tat-CEA and LLO, and both Tat-CEA and Tat-LLO, antibody titer to CEA and LLO, cytotoxic T lymphocyte activity and the frequency of IFN-${\gamma}$ producing T lymphocytes were measured. Results: Immunization using DC pulsed with both Tat-CEA and Tat-LLO protein showed the increasement of production of CEA-specific antibody in serum, cytotoxic T lymphocyte activity, the frequency of IFN-${\gamma}$ secreting T cells, compared with DC pulsed with both Tat-CEA and LLO. Furthermore the ratio of CD8+T cell to $CD4^+$ cell among CEA-specific T cells was increased in group pulsed with both Tat-CEA and Tat-LLO. Conclusion: These results suggested that DC vaccine using Tat-LLO could be used for the development of effective immunotherapy for the treatment of tumor.

• Biomolecules & Therapeutics
• /
• v.13 no.3
• /
• pp.174-180
• /
• 2005

Antigen presenting cells (APCs), dendritic cells (DCs) and macrophages, playa critical role not only in the initiation of immune responses, but also in the induction of immune tolerance. In an effort to regulate immune responses through the modulation of APC function, we searched for and characterized APC function modulators from natural products. Bifidobacterium pseudocatenulatum SPM1204 (SPM1204) isolated from feces of healthy Korean in the age of 20s was used in this experiment. DCs and macrophages were cultured in the presence of supernatants of SPM 1204 and then examined for their activities for the presentation exogenous antigen in association with major histocompatibility complexes (MHC) and macrophage activation. SPM1204 increased class I MHC-restricted presentation of exogenous antigen (cross-presentation) in a DC cell line, DC2.4 cells. The RAW 264.7 cell line was used to test the nonspecific effect of immune reinforcement of SPM1204 as a source of biological regulating modulator for the macrophage activation, include nitric oxide (NO) production and cytokine production. Results showed that the production of NO, tumor necrosis factor (TNF)-$\alpha$, interleukin 1 (IL-1)-$\beta$ and morphological changes in macrophages were largely affected by SPM1204 in a dose-dependent manner. Our results demonstrated that SPM1204 promote cross-presentation of dendritic cells as well as the induction of NO, TNF-$\alpha$ production, and activation of macrophage.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.3
• /
• pp.169-173
• /
• 2009

Ginsan, a Panax ginseng polysaccharide that contains glucopyranoside and fructofuranoside, has immunomodulatory effects. Although several biologic studies of ginsan have been performed, its effects on dendritic cells (DCs), which are antigen-presenting cells of the immune system, have not been studied. We investigated the immunomodulatory effects of ginsan on DCs. Ginsan had little effect on DC viability, even when used at high concentrations. Ginsan markedly increased the levels of production by DCs of IL-12 and TNF-${\alpha}$, as measured by ELISA. To examine the maturation-inducing activity of ginsan, we measured the surface expression levels of the maturation markers MHC class II and CD86 (B7.2) on DCs. It is interesting that ginsan profoundly enhanced the expression of CD86 on DC surfaces, whereas it increased that of MHC class II only marginally. In $^3H$-thymidine incorporation assays, ginsan-treated DCs stimulated significantly higher proliferation of allogeneic $CD4^+$ T lymphocytes than did medium-treated DCs. Taken together, our data demonstrate that ginsan stimulates DCs by inducing maturation. Because DCs are critical antigen-presenting cells in immune responses, this study provides valuable information on the activities of ginsan.

• BMB Reports
• /
• v.48 no.5
• /
• pp.283-288
• /
• 2015

We found that resveratrol enhances interferon (IFN)-γ-induced tryptophanyl-tRNA-synthetase (TTS) expression in bone marrow-derived dendritic cells (BMDCs). Resveratrol-induced TTS expression is associated with glycogen synthase kinase-3β (GSK-3β) activity. In addition, we found that resveratrol regulates naive CD8⁺ T-cell polarization by modulating GSK-3β activity in IFN-γ-stimulated BMDCs, and that resveratol induces upregulation of TTS in CD8⁺ T-cells in the in vivo tumor environment. Taken together, resveratrol upregulates IFN-γ-induced TTS expression in a GSK-3β-dependent manner, and this TTS modulation is crucial for DC-mediated T-cell modulation. [BMB Reports 2015; 48(5): 283-288]

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.202.3-203
• /
• 2003

Calcineurin inhibitors, cyclosporine A (CsA) and tacrolimus (FK506), have been studied extensively regarding their effects on T lymphocytes, but their effects on dendritic cells (DC) are relatively unknown. DC can really capture Ag from dead and dying cells for presentation to MHC class I-restricted CTL. The main targets for the immunosuppressive calcinerin inhibitors, FK506 and CsA. have been considered to be activated T cells, but not antigen presenting cells (APCs). (omitted)

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.3109-3116
• /
• 2013

The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Antitumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.

• IMMUNE NETWORK
• /
• v.14 no.3
• /
• pp.128-137
• /
• 2014

Respiratory viruses can induce acute respiratory disease. Clinical symptoms and manifestations are dependent on interactions between the virus and host immune system. Dendritic cells (DCs), along with alveolar macrophages, constitute the first line of sentinel cells in the innate immune response against respiratory viral infection. DCs play an essential role in regulating the immune response by bridging innate and adaptive immunity. In the steady state, lung DCs can be subdivided into $CD103^+$ conventional DCs (cDCs), $CD11b^+$ cDCs, and plasmacytoid DCs (pDCs). In the inflammatory state, like a respiratory viral infection, monocyte-derived DCs (moDCs) are recruited to the lung. In inflammatory lung, discrimination between moDCs and $CD11b^+$ DCs in the inflamed lung has been a critical challenge in understanding their role in the antiviral response. In particular, $CD103^+$ cDCs migrate from the intraepithelial base to the draining mediastinal lymph nodes to primarily induce the $CD8^+$ T cell response against the invading virus. Lymphoid $CD8{\alpha}^+$ cDCs, which have a developmental relationship with $CD103^+$ cDCs, also play an important role in viral antigen presentation. Moreover, pDCs have been reported to promote an antiviral response by inducing type I interferon production rather than adaptive immunity. However, the role of these cells in respiratory infections remains unclear. These different DC subsets have functional specialization against respiratory viral infection. Under certain viral infection, contextually controlling the balance of these specialized DC subsets is important for an effective immune response and maintenance of homeostasis.

• Biomolecules & Therapeutics
• /
• v.20 no.4
• /
• pp.399-405
• /
• 2012

Silver nanoparticles (AgNPs) are widely used nanoparticles and they are mainly used in antibacterial and personal care products. In this study, we evaluated the effect of AgNPs on cell death induction in the murine dendritic cell line DC2.4. DC2.4 cells exposed to AgNPs showed a marked decrease in cell viability and an induction of lactate dehydrogenase (LDH) leakage in a time- and dose-dependent manner. In addition, AgNPs promoted reactive oxygen species (ROS)-dependent apoptosis and AgNP-induced ROS triggered a decrease in mitochondrial membrane potential. The activation of the intracellular signal transduction pathway was also observed in cells cultured with AgNPs. Taken together, our data demonstrate that AgNPs are able to induce a cytotoxic effect in DCs through ROS generation. This study provides important information about the safety of AgNPs that may help in guiding the development of nanotechnology applications.

• Journal of Life Science
• /
• v.21 no.12
• /
• pp.1789-1794
• /
• 2011

Dendritic cells (DCs) are professional antigen-presenting cells playing key roles in immune sentinels as initiators of T-cell responses against microbial pathogens and tumors. Sarijang, a folk sauce containing extracts of Rhynchosia nulubilis, Ulmus davidiana roots, Allium sativum, and Rhus Verniaiflura bark, has been used as a nonspecific immunostimulant for cancer patients. However, little is known about its immunomodulating effects or their mechanisms. In this study, we investigated whether sarijang induces phenotypic and functional maturation of DCs. For this study, murine bone marrow-derived myeloid DCs were cultured in the presence of interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF), and the generated immature DCs were stimulated with sarijang or lipopolysaccharide (LPS). Our data indicated that sarijang significantly enhanced the expression of co-stimulatory molecules (CD80 and CD86) as well as major histocompatibility complex (MHC) II, as did LPS. The results provide new insight into the immunopharmacology of sarijang and suggest a novel approach to the manipulation of DC for therapeutic application.