• IMMUNE NETWORK
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• 제16권1호
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• pp.52-60
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• 2016

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that bridge innate and adaptive immune responses, thereby leading to immune activation. DCs have been known to recognize pathogen-associated molecular patterns such as lipopolysaccharides (LPS) and nucleic acids via their pattern recognition receptors, which trigger signaling of their maturation and effector functions. Furthermore, DCs take up and process antigens as a form of peptide loaded on the major histocompatibility complex (MHC) and present them to T cells, which are responsible for the adaptive immune response. Conversely, DCs can also play a role in inducing immune suppression under specific circumstances. From this perspective, the role of DCs is related to tolerance rather than immunity. Immunologists refer to these special DCs as tolerogenic DCs (tolDCs). However, the definition of tolDCs is controversial, and there is limited information on their development and characteristics. In this review, we discuss the current concept of tolDCs, cutting-edge methods for generating tolDCs in vitro, and future applications of tolDCs, including clinical use.

• 대한수의학회지
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• 제43권4호
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• pp.607-613
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• 2003

Dendritic cells (DCs) play an essential role in a variety of immune reactions involving $CD4^+$ T cells and have been used to enhance tumor-specific immune responses. Immunosuppression in patients with cancer includes the downregulation of function and number of DCs. Although DCs have been studied, the apoptosis of Des induced by anticancer drugs for chemotherapy remains largely uncharacterized. This study demonstrated that GM-CSF protects DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. After 6 - 10 days culture, DCs were characterized by specific surface marker, CD11c and MHC class II. MTT assay revealed that GM-CSF significantly enhanced the viability of DCs treated with 5-FU or mitomycin C. The percentage of dead cells of DCs was determined by cell size using FACScan and GM-CSF was clearly effective. However, GM-CSF did not increase the expression of MHC class II on viable DCs gated, suggesting that GM-CSF may differentially regulate critical factors involved in the function of DCs. For the quantitative analysis of apoptosis, annexin V-FITC staining was performed. 5-FU induced the apoptosis of DCs and GM-CSF significantly protects DCs from 5-FU-induced apoptosis. Taken together, the results in this study that GM-CSF has an anti-apoptosis effect on DCs may provide patients with cancer with clinical benefits to overcome the immunosuppression induced by the decrease of number and functional insufficiency of DCs.

• IMMUNE NETWORK
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• 제14권3호
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• pp.128-137
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• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제16권4호
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• pp.243-247
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• 2012

Recent studies suggest that immunization with autologous dendritic cells (DCs) results in protective immunity and rejection of established tumors in various human malignancies. The purpose of this study is to determine whether DCs are generated from peripheral blood mononuclear cells (PBMNs) by using cytokines such as F1t-3 ligand (FL), granulocyte macrophage-colony stimulating factor (GM-CSF), IL-4, and TNF-${\alpha}$, and whether cytotoxic T cells activated against the thyroid cancer tissues by the DCs. Peripheral blood was obtained from 2 patients with thyroid cancer. DCs were established from PBMNs by culturing in the presence of FL, GM-CSF, IL-4, and TNF-${\alpha}$ for 14 days. At day 14, the differentiated DCs was analyzed morphologically. The immunophenotypic features of DCs such as CDla, CD83, and CD86 were analyzed by immunofluorelescence microscopy. At day 18, DCs and T cells were incubated with thyroid cancer tissues or normal thyroid tissues for additional 4 days, respectively. DCs generated from the PBMNs showed the typical morphology of DCs. Activated cytotoxic T lymphocytes (CTLs) were observed also. DCs and the CTLs were attached to the cancer tissues on scanning electron microscope. The DCs activated the CTLs, which able to specifically attack the thyroid cancer. This study provides morphologic evidence that the coculture of T cells/cancer tissues activated the T cells and differentiated CTLs. The CTLs tightly adhered to cancer tissues and lysed cancer tissues vigorously. Therefore DCs could be used as potential vaccines in the immunotherapy.

• 한국운동역학회지
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• 제32권4호
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• pp.121-127
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• 2022

Objective: The purpose of this study was to investigate potential effects of transcranial direct current stimulation (tDCS) on bimanual force control capabilities in healthy young adults. Method: Eighteen right-handed healthy young adults (10 females and 8 males; age: 23.55 ± 3.56 yrs) participated in this crossover design study. All participants were randomly allocated to both active-tDCS and sham-tDCS conditions, respectively. While receiving 20 min of active- or sham-tDCS interventions, all participants performed bimanual isometric force control tasks at four submaximal targeted force levels (i.e., 5%, 10%, 15, and 20% of maximal voluntary contraction: MVC). To compare bimanual force control capabilities including force accuracy, variability, and regularity between active-tDCS and sham-tDCS conditions, we conducted two-way repeated measures ANOVAs (2 × 4; tDCS condition × Force levels). Results: We found no significant difference in baseline MVC between active-tDCS and sham-tDCS conditions. Moreover, our findings revealed that providing bilateral tDCS including anodal tDCS on left primary motor cortex (M1) and cathodal on right M1 while conducting bimanual force control trials significantly decreased force variability and regularity at 5%MVC. Conclusion: These findings suggest that providing bilateral tDCS on M1 areas may improve bimanual force control capabilities at a relatively low targeted force level.

• The Journal of Korean Physical Therapy
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• 제21권4호
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• pp.65-71
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• 2009

Purpose: Transcranial direct current stimulation (tDCS) is a useful method for modulating the brain activity. This study compared the effect of continuous and interrupted tDCS using the change in the movement related cortical potential. Methods: Thirty healthy participants (male: 18 and female: 12) were assigned randomly to three groups; sham tDCS, continuous tDCS, which the current continuously flowed for 10 minutes, and interrupted tDCS, which the interrupted current flowed for 10 minutes (repetition: 4sec stimulation and 5sec rest) at an intensity of 1mA with anodal polarity. The effect of tDCS on the right primary motor area was measured from the movement related cortical potential (MRCP) before and after the experiment. MRCP consisted of the bereitshaftspotential (BP) and negative slope potential (NS) at Cz and C4. Results: Continuous and interrupted tDCS showed a significant difference in the changes in the BP, NS at Cz and C4 compared to the sham tDCS. However, there was no significant difference between the continuous tDCS and interrupted tDCS. Conclusion: The change in cortical activity by continuous and interrupted tDCS results from an improvement in the MRCP. An interrupted tDCS may be a safe and useful modality for stimulating the cortical region.

• Gut and Liver
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• 제12권6호
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• pp.664-673
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• 2018

Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.

• IMMUNE NETWORK
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• 제5권2호
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• pp.105-109
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• 2005

Background: Dendritic cells (DCs) are the most potent APCs (antigen-presenting cells) and playa critical role in immune responses. Galectin-3 is a biological lectin with a beta-galactoside binding affinity. Recently, proteomic analysis revealed the presence of galectin-3 in the exosome of mature DCs. However, the expression and function of galectin-3 in DCs remains unclear yet. Methods: We used bone marrow-derived DCs of mouse and showed the expression of galectin-3 in DCs by using flow cytometry analysis and Western blot analysis. Results: Galectin-3 was determined as single band of 35 kDa in Western blot analysis. Flow cytometry analysis showed the major growth factor for DCs, granulocyte-macrophage colony stimulating factor (GM-CSF) and maturing agents, anti-CD40 monoclonal antibody (mAb) and lipopolysaccharide (LPS) consistently increased the intracellular expression of galectin-3 in DCs compared to medium alone. In addition, DCs treated with maturing agents did marginally express galectin-3 on their surface. Conclusion: This study suggests that galectin-3 in DCs may be regulated by critical factors for DC function.

• The Korean Journal of Physiology and Pharmacology
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• 제27권5호
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• pp.471-479
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• 2023

Disulfiram (DSF), a medication for alcoholism, has recently been used as a repurposing drug owing to its anticancer effects. Despite the crucial role of dendritic cells (DCs) in immune homeostasis and cancer therapy, the effects of DSF on the survival and function of DCs have not yet been studied. Therefore, we treated bone marrow-derived DCs with DSF and lipopolysaccharide (LPS) and performed various analyses. DCs are resistant to DSF and less cytotoxic than bone marrow cells and spleen cells. The viability and metabolic activity of DCs hardly decreased after treatment with DSF in the absence or presence of LPS. DSF did not alter the expression of surface markers (MHC II, CD86, CD40, and CD54), antigen uptake capability, or the antigen-presenting ability of LPS-treated DCs. DSF decreased the production of interleukin (IL)-12/23 (p40), but not IL-6 or tumor necrosis factor-α, in LPS-treated DCs. We considered the granulocyte-macrophage colony-stimulating factor (GM-CSF) as a factor to make DCs resistant to DSF-induced cytotoxicity. The resistance of DCs to DSF decreased when GM-CSF was not given or its signaling was inhibited. Also, GM-CSF upregulated the expression of a transcription factor XBP-1 which is essential for DCs' survival. This study demonstrated for the first time that DSF did not alter the function of DCs, had low cytotoxicity, and induced differential cytokine production.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.255-259
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• 2003

Dendritic cells (DCs) play a critical role in various immune responses involving $CD4^+$ T cells and have been used to generate anti-tumor immunity. Chemotherapy induces severe side effects including immunosuppression in patients with cancer. Although immunosuppression has been studied, the effects of anticancer drugs on DCs are not fully determined. In this study, we demonstrated that CD40 activation strongly protected DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. DCspecific surface markers, including CD11c and major histocompatibility complex (MHC) class II, were used for identifying DCs. CD 40 activation with anti-CD40 mAb significantly enhanced the viability of DCs treated with 5-FU or mitomycin C, assayed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Fluorescence staining and analysis clearly confirmed the enhancing effect of anti-CD40 mAb on the viability of DCs, suggesting that CD40 activation may transduce critical signals for the viability of DCs. Annexin V staining assay showed that CD40 significantly protected DCs from 5-FU or mitomycin C-induced apoptosis. Taken together, this study shows that CD40 activation with anti-CD40 mAb has strong anti-apoptosis effect on DCs, suggesting that CD40 activation may overcome the immunosuppression, especially downregulation of number and function of DCs in chemotherapy-treated cancer patients.