• BMB Reports
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• v.47 no.2
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• pp.115-120
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• 2014

In this study, we show that Mycobacterium avium subsp. paratuberculosis MAP1305 induces the maturation of bone marrow-derived dendritic cells (BMDCs), a representative antigen presenting cell (APC). MAP1305 protein induces DC maturation and the production of pro-inflammatory cytokines (Interleukin (IL)-6), tumor necrosis factor (TNF)-${\alpha}$, and IL-$1{\beta}$) through Toll like receptor-4 (TLR-4) signaling by directly binding with TLR4. MAP1305 activates the phosphorylation of MAPKs, such as ERK, p38MAPK, and JNK, which is essential for DC maturation. Furthermore, MAP1305-treated DCs transform naive T cells to polarized $CD4^+$ and $CD8^+$ T cells, thus indicating a key role for this protein in the Th1 polarization of the resulting immune response. Taken together, M. avium subsp. paratuberculosis MAP1305 is important for the regulation of innate immune response through DC-mediated proliferation of $CD4^+$ and $CD8^+$ T cells.

• Animal cells and systems
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• v.16 no.3
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• pp.215-223
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• 2012

Recently it has been reported that immunization with heat-killed tumor cells (HK vaccine) induces anti-tumor immune responses in mice. To investigate how HKvaccine elicits anti-tumor specific adaptive immunity, we examined the effect of HK vaccination on innate immune cells such as dendritic cells (DCs), which are essential for the generation of adaptive immunity. Upon stimulation with HK vaccine, DCs matured to promote not only the upregulation of co-stimulatory molecules but also secretion of cytokine IL12. Furthermore, HK vaccine-treated DCs migrated more efficiently to draining lymph nodes compared with untreated ones. Taken together, HK vaccine can be useful as an adjuvant to activate DCs for anti-tumor immune responses.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.206-212
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• 2005

Purpose: Angiogenesis has a critical role in tumor proliferation, invasion, and metastasis. In gastric cancer, tumor-associated macrophages and mast cells produce angiogenic factors such as VEGF, that inhibit the functional maturation of dendritic cells. The aim of this study is to identify tumor-associated macrophages, mast cells, dendritic cell infiltrations, and microvessel densities (MVD) to investigate the relationship between them and the prognosis for gastric-cancer patients. Materials and Methods: The subjects were 79 patients selected from those who had undergone a curative gastric resection for stomach cancer. With them, Immune-histochemical staining was done using CD34 for the MVD, CD68 antigen for macrophages, and S-100 protein for dendritic cells, and toluidine blue staining was done for mast cells. Results: Macrophage infiltration showed a statistically significant positive correlation with histologic differentiation and a negative correlation with invasion depth, nodal metastasis, and stage. S-100 (+) dendritic cells and mast cells had no significant correlations with histologic differentiation, invasion depth, nodal metastasis, distant metastasis, stage, and MVD. As survival, no statistically significant differences were seen between the variables. Conclusion: Tumor-associated macrophages should be evaluated as possible prognostic markers in gastric-cancer patients.

• IMMUNE NETWORK
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• v.8 no.4
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• pp.137-142
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• 2008

Background: CD11c, also known as integrin alpha x, is one of the optimum markers of dendritic cells. However, the regulation of the CD11c expression in mouse has not been identified yet. In this study, in order to analyze the regulation of CD11c expression, the promoter of CD11c was cloned and characterized. Methods: To identify the promoter portion, various sizes of what are considered to be CD11c promoter fragments was amplified by polymerase chain reaction (PCR), using mouse genomic DNA as a template. After sequence was obtained, these fragments were transfected into various cell lines including mouse dendritic cell lines such as JAWSII and DC2.4 and L929 as control cell line.. The promoter activity of three promoter fragments was measured and compared by luciferase activity in the transfected cells. Results: Three clones with size of 1kb, 3kb and 6kb were obtained from mouse genomic DNA. Flow cytometry analysis of JAWSII cells revealed that 52% of the cells expressed CD11c, which was confirmed by RT-PCR analysis. On the contrary, L929 and DC 2.4 cells did not express CD11c. The CD11c+ JAWSII cells were enriched from 52% to 90% with cell sorter. The comparative luciferase activity analyisis demonstrated that the region responsible for tissue specific expression was contained within -3 kb and the clone with size of 3 kb particularly showed higher luciferase activity than 6 kb and 1 kb clones. Conclusion: The CD11c promoter region containing the region responsible for tissue specificity was successfully cloned and -3 kb region showed the highest activity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.611-616
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• 2014

Objectives: Dendritic cell (DC)-based tumor immunotherapy needs an immunogenic tumor associated antigen (TAA) and an effective approach for its presentation to lymphocytes. In this study we explored whether transduction of DCs with lentiviruses (LVs) expressing the human interleukin-12 gene could stimulate antigen-specific cytotoxic T cells (CTLs) against human lung cancer cells in vitro. Methods: Peripheral blood monocyte-derived DCs were transduced with a lentiviral vector encoding human IL-12 gene (LV-12). The anticipated target of the human IL-12 gene was detected by RT-PCR. The concentration of IL-12 in the culture supernatant of DCs was measured by ELISA.Transduction efficiencies and CD83 phenotypes of DCs were assessed by flow cytometry. DCs were pulsed with tumor antigen of lung cancer cells (DC+Ag) and transduced with LV-12 (DC-LV-12+Ag). Stimulation of T lymphocyte proliferation by DCs and activation of cytotoxic T-lymphocytes (CTL) stimulated by LV-12 transduced DCs pulsed with tumor antigen against A549 lung cancer cells were assessed with methyl thiazolyltetrazolium (MTT). Results: A recombinant lentivirus expressing the IL-12 gene was successfully constructed. DC transduced with LV-12 produced higher levels of IL-12 and expressed higher levels of CD83 than non-transduced. The DC modified by interleukin -12 gene and pulsed with tumor antigen demonstrated good stimulation of lymphocyte proliferation, induction of antigen-specific cytotoxic T lymphocytes and antitumor effects. Conclusions: Dendritic cells transduced with a lentivirus-mediated interleukin-12 gene have an enhanced ability to kill lung cancer cells through promoting T lymphocyte proliferation and cytotoxicity.

• IMMUNE NETWORK
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• v.13 no.5
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• pp.218-221
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• 2013

CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although ${\alpha}$-galactosylceramide (${\alpha}$-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-${\gamma}$ by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.

• IMMUNE NETWORK
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• v.15 no.3
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• pp.111-120
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• 2015

Dendritic cells (DCs) play a significant role in establishing self-tolerance through their ability to present self-antigens to developing T cells in the thymus. DCs are predominantly localized in the medullary region of thymus and present a broad range of self-antigens, which include tissue-restricted antigens expressed and transferred from medullary thymic epithelial cells, circulating antigens directly captured by thymic DCs through coticomedullary junction blood vessels, and peripheral tissue antigens captured and transported by peripheral tissue DCs homing to the thymus. When antigen-presenting DCs make a high affinity interaction with antigen-specific thymocytes, this interaction drives the interacting thymocytes to death, a process often referred to as negative selection, which fundamentally blocks the self-reactive thymocytes from differentiating into mature T cells. Alternatively, the interacting thymocytes differentiate into the regulatory T (Treg) cells, a distinct T cell subset with potent immune suppressive activities. The specific mechanisms by which thymic DCs differentiate Treg cells have been proposed by several laboratories. Here, we review the literatures that elucidate the contribution of thymic DCs to negative selection and Treg cell differentiation, and discusses its potential mechanisms and future directions.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.364-367
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• 2011

Background: Prostaglandins (PGs) play pathogenic and protective roles in inflammatory diseases. The novel concept of PGs as immune modulators is being documented by several investigators. By establishing an in vitro experimental model containing human follicular dendritic cell-like cells, HK cells, we reported that HK cells produce prostaglandin $E_2$ ($PGE_2$) and prostaglandin $I_2$ ($PGI_2$) and that these PGs regulate biological functions of T and B cells. Methods: To investigate the respective contribution of cyclooxygenase-1 (COX-1) and COX-2 to $PGE_2$ and $PGI_2$ production in HK cells, we performed siRNA technology to knock down COX enzymes and examined the effect on PG production. Results: Both $PGE_2$ and $PGI_2$ productions were almost completely inhibited by the depletion of COX-2. In contrast, COX-1 knockdown did not significantly affect PG production induced by lipopolysaccharide (LPS). Conclusion: The current results suggest that mPGES-1 and PGIS are coupled with COX-2 but not with COX-1 in human follicular dendritic cell (FDC) and may help understand the potential effects of selective COX inhibitors on the humoral immunity.

• Proceedings of the Zoological Society Korea Conference
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• 1996.10a
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• pp.138.1-138
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• 1996

No Abstract, See Full Text

• Tuberculosis and Respiratory Diseases
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• v.60 no.5
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• pp.523-531
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• 2006

Background : Cervical tuberculous lymphadenopathy is a very common disease with a similar incidence to pulmonary tuberculosis. Dendritic cells play a role of initial antigen presentation of this illness. Nevertheless, the precise role of these antigen-presenting cells according to the clinical features in unclear. The aim of this study was to determine the clinical implication of dendritic cell infiltration in the cervical lymph nodes. Methods : A review of the clinical characteristics was carried out retrospectively based on the clinical records and radiography. Immunohistochemical staining was performed on the available histology specimens of 72 cases using the S-100b polyclonal antibody for dendritic cells. The number of dendritic cells with tuberculous granuloma were determined. A $X^2$ test, unpaired T test and multiple logistic regression analysis were performed. Results : Thirty percent of subjects had previous or concurrent pulmonary TB. Twenty one percent of cases showed a positive reaction on the AFB stain. Within a granuloma, the number of infiltrated dendritic cells was $113.0{\pm}7.0$. The incidence of fever and cough decreased with increasing infiltration of dendritic cells Multivariate regression analysis showed that the infiltration of dendritic cells could significantly contribute to fever. Conclusion : Overall, dendritic cells can control a Mycobacterium tuberculosis infection and modulate the immune response, as well as resolve the clinical manifestations of TB lymphadenopathy.