• Molecules and Cells
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• v.38 no.1
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• pp.89-94
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• 2015

The shape and activity of mitochondria are tightly regulated by fusion and fission processes that are essential for maintaining normal cellular function. However, little is known about the involvement of mitochondrial dynamics in the development of the immune system. In this study, we demonstrate that mitochondrial dynamics play a role in the differentiation and migration of immature dendritic cells (imDCs). We show that mitochondrial elongation is induced during GM-CSF-stimulated differentiation of bone marrow progenitors to imDCs accompanied by upregulation of mitochondrial fusion proteins. These processes precede the changes in mitochondrial morphology and connectivity that occur during differentiation. Mfn2 and OPA1, but not Mfn1, are transcriptionally upregulated during differentiation; however, knockdown of Mfn2 and OPA1 does not induce any change in expression of CD11c, CDC80, or CD86. Notably, knockdown of Mfn2 or OPA1 by siRNA in imDCs significantly reduces CCR7 expression and CCL19-mediated migration. These results suggest that the mitochondrial fusion-related proteins Mfn2 and OPA1 are upregulated during bone marrow progenitor differentiation and promote the migration of imDCs by regulating the expression of CCR7.

• Proceedings of the KACD Conference
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• 2003.11a
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• pp.602-602
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• 2003

I. Objectives It is reported that there are complements and immunogloblins in serum from dental pulp in dentinal tubules, and it is thought that dental caries bacteria is opsonized by these serum ingredients, and it is presented by dendritic cells(DCs) in dental pulp. So, we examined whether a maturational difference of DCs occured when S. mutans was opsonized. II. Materials and Methods PBMC was divided from normal human peripheral blood and collected CD14 positive cells by magnetic beads system. Adherent cells were incubated in 5% FCS-RPMI medium included GM-CSF, IL-4 for seven days.(omitted)

• Journal of Ginseng Research
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• v.36 no.4
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• pp.375-382
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• 2012

Ginsenoside Rp1 (G-Rp1) is a saponin derivate that provides anti-metastatic activities through inhibition of the NF-${\kappa}B$ pathway. In this study, we examined the effects of G-Rp1 on regulatory T cell (Treg) activation. After treatment of splenocytes with G-Rp1, Tregs exhibited upregulation of IL-10 expression, and along with dendritic cells (DCs), these Tregs showed increased cell number compared to other cell populations. The effect of G-Rp1 on Treg number was augmented in the presence of lipopolysaccharide (LPS), which mimics pathological changes that occur during inflammation. However, depletion of DCs prevented the increase in Treg number in the presence of G-Rp1 and/or LPS. In addition, G-Rp1 promoted the differentiation of the memory types of $CD4^+Foxp3^+CD62L^{low}$ Tregs rather than the generation of new Tregs. In vivo experiments also demonstrated that Tregs and DCs from mice that were fed G-Rp1 for 7 d and then injected with LPS exhibited increased activation compared with those from mice that were injected with LPS alone. Expression of TGF-${\beta}$ and CTLA4 in Tregs was increased, and upregulation of IL-2 and CD80/CD86 expression by DCs affected the suppressive function of Tregs through IL-2 receptors and CTLA4. These data demonstrate that G-Rp1 exerts anti-inflammatory effects by activating Tregs in vitro and in vivo.

• Journal of Periodontal and Implant Science
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• v.44 no.5
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• pp.235-241
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• 2014

Purpose: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are known to play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, and graft rejection. Dendritic cells (DCs) are considered the major antigen-presenting cells (APCs) for initiating these T-cell immune responses, of which $CD103^+$ DCs are derived from precursor human peripheral blood mononuclear cells (PBMCs). The aim of the present study was to evaluate the capacity of these PBMC-derived $CD103^+$ DCs to promote the differentiation of antigen-specific Tregs. Methods: Monocyte-derived DCs were induced from $CD14^+$ monocytes from the PBMCs of 10 healthy subjects. Once the $CD103^+$ DCs were purified, the cell population was enriched by adding retinoic acid (RA). Peptide numbers 14 and 19 of Porphyromonas gingivalis heat shock protein 60 (HSP60) were synthesized to pulse $CD103^+$ DCs as a tool for presenting the peptide antigens to stimulate $CD3^+$ T cells that were isolated from human PBMC. Exogenous interleukin 2 was added as a coculture supplement. The antigen-specific T-cell lines established were phenotypically identified for their expression of CD4, CD25, or Foxp3. Results: When PBMCs were used as APCs, they demonstrated only a marginal capacity to stimulate peptide-specific Tregs, whereas $CD103^+$ DCs showed a potent antigen presenting capability to promote the peptide-specific Tregs, especially for peptide 14. RA enhanced the conversion of $CD103^+$ DCs, which paralleled the antigen-specific Treg-stimulating effect, though the differences failed to reach statistical significance. Conclusions: We demonstrated that $CD103^+$ DCs can promote antigen-specific Tregs from naive T cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA was an effective reagent that induces mature DCs with the typical phenotypic expression of CD103 that demonstrated the functional capability to promote antigen-specific Tregs.

• Journal of Korean Neurosurgical Society
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• v.38 no.2
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• pp.126-131
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• 2005

Objective : The choice of tumor antigen for dendritic cell[DC]-loading has still been an unresolved problem in the DC-based vaccine strategies against malignant gliomas that has not been found well-characterized tumor specific antigens. In this study, we compare tumor-specific T cell response induced by glioma apoptotic body[GAB]-pulsed DCs to response induced by glioma cell lysate-pulsed ones quantitatively. Methods : DCs generated in the presence of granulocyte macrophage-colony stimulating factor and interleukin[IL]-4 from peripheral blood mononuclear cells[PBMCs] of HLA-A2 positive healthy donors were cultured. Each GABs and glioma cell lysate generated from HLA-A2 positive T98G glioblastoma cells were co-incubated with DCs. $CD8^+$ T lymphocytes isolated from PBMCs of same donors were cultured in media containing IL-2 and either stimulated by GAB- or lysate-pulsed DCs three times at a weekly interval. The interferon[IFN]-${\gamma}$ concentrations of each cell culture supernate were measured by enzyme immunoassay technique. Cytolytic activity of the generated cytotoxic $CD8^+$ T cells either stimulated with GAB- or lysate-pulsed DCs was determined by a standard 4-h $^{51}Cr$-release assay. Results : IFN-${\gamma}$ production and cytolytic activity of effector T cells stimulated by GAB-pulsed DCs were significantly higher than those of T cells stimulated by lysate-pulsed ones. Conclusion : These results indicate the choice of antigen is a critical determinant in the induction of antitumor immunity against malignant glioma. Antigen preparations from GABs represent a promising alternative to glioma cell lysate in DC-based glioma vaccine strategies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5909-5916
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• 2014

Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in the development of cervical cancer. Since mature dendritic cells (DCs) are potent antigen-presenting cells (APC), they could be primed by HPV antigens against cervical cancers. In this study we were able to generate, maintain and characterize, both phenotypically and functionally, patient specific dendritic cells in vitro. A randomized Phase I trial with three arms - saline control (arm I), unprimed mature DC (arm II) and autologous tumor lysate primed mature DC (arm III) and fourteen patients was conducted. According to WHO criteria, grade 0 or grade one toxicity was observed in three patients. One patient who received tumor lysate primed dendritic cells and later cis-platin chemotherapy showed a complete clinical response of her large metastatic disease and remained disease free for more than 72 months. Our findings indicate that DC vaccines hold promise as adjuvant sfor cervical cancer treatment and further studies to improve their efficacy need to be conducted.

• IMMUNE NETWORK
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• v.16 no.1
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• pp.33-43
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• 2016

Cell-penetrating peptides (CPPs) are short amino acids that have been widely used to deliver macromolecules such as proteins, peptides, DNA, or RNA, to control cellular behavior for therapeutic purposes. CPPs have been used to treat immunological diseases through the delivery of immune modulatory molecules in vivo. Their intracellular delivery efficiency is highly synergistic with the cellular characteristics of the dendritic cells (DCs), which actively uptake foreign antigens. DC-based vaccines are primarily generated by pulsing DCs ex vivo with various immunomodulatory antigens. CPP conjugation to antigens would increase DC uptake as well as antigen processing and presentation on both MHC class II and MHC class I molecules, leading to antigen specific CD4⁺ and CD8⁺ T cell responses. CPP-antigen based DC vaccination is considered a promising tool for cancer immunotherapy due to the enhanced CTL response. In this review, we discuss the various applications of CPPs in immune modulation and DC vaccination, and highlight the advantages and limitations of the current CPP-based DC vaccination.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3109-3116
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• 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
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• v.22 no.2
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• pp.16.1-16.20
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• 2022

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes (LM). Fasting induced an increased number of CD103⁺CD11b^- DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103⁺CD11b^- DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-β2 and Aldh1a2 expression in CD103⁺CD11b^- DCs in mice infected with LM might affect to increase of Foxp3⁺ regulatory T cells. Changes of major subset of DCs from CD103⁺ to CD103^- may induce the increase of IFN-γ-producing cells with forming Th1-biased environment. Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.412-415
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• 2011

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the $H-2K^b$-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.