• Hanyang Medical Reviews
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• v.33 no.1
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• pp.10-16
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• 2013

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

• Clinical and Experimental Pediatrics
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• v.58 no.5
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• pp.178-182
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• 2015

Purpose: The purpose of this study was to determine the frequency of $CD4^+CD25^+FoxP3^+$ regulatory T cells (Treg) in the peripheral blood of patients with childhood chronic immune thrombocytopenic purpura (ITP) exhibiting thrombocytopenia and spontaneous remission. The findings of this study indicate the possibility of predicting spontaneous recovery and pathogenesis of childhood chronic ITP. Methods: Eleven children with chronic ITP (seven thrombocytopenic and four spontaneous remission cases; mean age, 8.8 years; range, 1.7-14.9 years) were enrolled in this study. Five healthy children and eight healthy adults were included as controls. The frequency of Treg was evaluated by flow cytometry in the peripheral blood. Results: In this study, four patients (36%) achieved spontaneous remission within 2.8 years (mean year; range, 1.0-4.4 years). The frequency of Treg was significantly lower in patients with persisting thrombocytopenia ($0.13%{\pm}0.09%$, P<0.05), than that in the patients with spontaneous remission ($0.30%{\pm}0.02%$), healthy adults controls ($0.55%{\pm}0.44%$), and healthy children controls ($0.46%{\pm}0.26%$). A significantly positive correlation was found between the frequency of Treg and the platelet count in children. Conclusion: These data suggest that a lower frequency of Treg contributes to the breakdown of self-tolerance, and may form the basis for future development of specific immunomodulatory therapies. Furthermore, Treg frequency has prognostic implication toward the natural course and long-term outcomes of childhood chronic ITP.

• International Journal of Oral Biology
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• v.34 no.3
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• pp.131-135
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• 2009

The sublingual locus has recently received great attention as a delivery site for various immunotherapies, including those that induce allergen-specific tolerance, and for vaccines that generate protective immunity. To further understand the immune functions of the human sublingual mucosa, we characterized the distribution of various immunocytes therein by immunohistochemistry. We identified professional antigen presenting cells (APCs), including Langerhans cells (LCs) and macrophages. $CD1a^+$ and $langerin^+$ LCs were further found to be distributed in the basal and supra-basal layers of the epithelium, and macrophages were identified in the lamina propria. HLA-$DR^+$ cells were observed in both the epithelium and the lamina propria, which mirrors the tissue distribution of LCs and macrophages within these tissues. $CD3^+$, $CD4^+$, and $CD8^+$ T cells were found to be distributed along the basal layer of the epithelium and also in the lamina propria. Although B cells, plasma cells, and $Foxp3^+$ regulatory T cells (Tregs) were only occasionally observed in the human sublingual mucosa in the absence of inflammation, they did show enrichment at inflammatory sites. Hence, we have further elucidated the immune cell component distribution in human sublingual mucosa.

• Korean Journal of Environmental Agriculture
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• v.16 no.2
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• pp.142-148
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• 1997

This study was performed to develop the biological treatment technology of wastewater polluted with heavy metals. Heavy metal-tolerant microorganisms, such as Pseudomonas putida, P. aeruginosa, P. chlororaphis and P. stutzeri possessing the ability to accumulate cadmium, lead, zinc and copper, respectively, were isolated from industrial wastewaters and mine wastewaters polluted with various heavy metals. The effect of competing ions and metabolic inhibitors on heavy metal accumulation in the cells was investigated. Heavy metal accumulation into cells was drastically decreased in the presence of competing cation, $Al^{3+}$, and also decreased, at a lesser extent, in the presence of competing anions, $CO_3\;^{2-}$ and $PO_4\;^{2-}$. But heavy metal accumulation was not influenced generally in the presence of the other rations and anions. The accumulation of Cd, Zn or Cu by Cd-, Zn- or Cu-tolerant microorganism was remarkably decreased in the presence of metabolic inhibitors, but the accumulation of Pb by Pb-tolerant microorganism was little affected in the presence of metabolic inhibitors. These results suggested that the accumulation of Cd, Zn or Cu by Cd-, Zn- or Cu-tolerant microorganism was concerned with the biological activity depending on energy, and the accumulation of Pb by Pb-tolerant microorganism depended on not the biological activity but the physical adsorption on the cell surface. Each heavy metal-tolerant microorganism also exhibited some ability to accumulate the other heavy metals in solution containing equal concentrations of cadmium, lead, zinc and copper, when measured at 48 hours after inoculation of the microorganisms, but the accumulation rates were somewhat low as compared to the accumulation rates of heavy metal fitting to each tolerance. These results suggested that the accumulation of each heavy metal by each heavy metal-tolerant microorganism was a selective accumulation process.

• Microbiology and Biotechnology Letters
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• v.26 no.1
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• pp.83-88
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• 1998

Heavy metal removal by Z. ramigera 115 and soluble slime polymer producing mutant Z. ramigera 115SLR was investigated. Both strains showed similar tolerance against $Cd^{2+}$, $Co^{2+}$, $Cu^{2+}$, $Ni^{2+}$ and $Fe^{2+}$. When cells were cultivated in the presence of 500 ppm $Cd^{2+}$, the mutant strain removed 1.5 fold more metal than the wild type did at same biomass. Metal adsorption capacities were in the order of Z. ramigera l15SLR polymer > Z. ramigera 115 polymer > Z. ramigera 115 cell >Z. ramigera l15SLR cell. The optimum pH for metal adsorption was 7.5. Langmuir and Freundlich isotherms indicated that Qmax and 1/n of Z. ramigera l15SLR polymer were 164.2 mg $Cd^{2+}$/g dw and 0.496, respectively. These results showed that the polymer of Z. ramigera l15SLR could be used as an effective metal adsorbate.

• Microbiology and Biotechnology Letters
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• v.32 no.4
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• pp.341-346
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• 2004

The quantification of the toxicological effects of the heavy metals such as Cu, Cd, Cr, Hg, and Zn on the growth of Escherichia coli was performed, and the variations of toxicwith exposure time were evaluated in adaptation procedure. The characteristics of growth inhibition on Escherichia coli by heavy metals were different with metal species, and critical concentration of each metal, which inhibited cell growth completely, were Cu of 3.5 mM, Zn of 2.5 mM, Cd of 1.5 mM, Cr of 1.2 mM, and Hg of 0.12 mM, respectively. The tolerance of E. coli against heavy metals, based on $EC_{50}$ values, increased in order of Cu > Zn > Cr > Cd > Hg. The slopes obtained from the relationship between ECso values and expose time corresponds to adaptability of test organisms to the toxicants. The adaptability of test organisms to the toxicants was much higher at higher slope values. Adaptability of E. coli on heavy metals increased in order to Zn > Cd > CU >> Cr> Hg.

• IMMUNE NETWORK
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• v.16 no.5
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• pp.281-285
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• 2016

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet b cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.371-381
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• 2018

Purpose: Immune suppression is common in patients with advanced breast cancer but the mechanisms underlying this phenomenon have not been sufficiently studied. In this study, we aimed to identify B7 family members that were able to predict the immune status of patients, and which may serve as potential targets for the treatment of breast cancer. We also aimed to identify microRNAs that may regulate the expression of B7 family members. Methods: The Cancer Genome Atlas data from 1,092 patients with breast cancer, including gene expression, microRNA expression and survival data, were used for statistical and survival analyses. Polymerase chain reaction and Western blot were used to measure messenger RNA and protein expression, respectively. Luciferase assay was used to investigate direct microRNA target. Results: Bioinformatic analysis predicted that microRNA (miR)-93, miR-195, miR-497, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and that they exert this function by targeting CD274, PDCD1LG2, and NCR3LG1. We chose CD274 for further investigations. We found that miR-195, miR-497, and CD274 expression levels were inversely correlated in MDA-MB-231 cells, and miR-195 and miR-497 expressions mimic inhibited CD274 expression in vitro. Mechanistic investigations demonstrated that miR-195 and miR-497 directly target CD274 3' untranslated region. Conclusion: Our data indicated that the level of B7 family members can predict the prognosis of breast cancer patients, and miR-195/miR-497 regulate CD274 expression in triple negative breast cancer. This regulation may further influence tumor progression and the immune tolerance mechanism in breast cancer and may be able to predict the effect of immunotherapy on patients.

• The Korean Journal of Mycology
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• v.36 no.2
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• pp.172-177
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• 2008

Mycelial growth of Pleurotus ostreatus isolates was examined on PDA media added with heavy metals to reveal effects of heavy metals on mycelial growth of the fungus. Cd and Cu strongly inhibited mycelial growth of three isolates of fungus tested. However, addition of $2{\sim}10\;mM$ Pb to growing media of white color mutant of fungus resulted in increase of the fungal growth rate. Addition of 2 mM Cr to the media resulted in increase of growth rate of the white color mutant and the dark color mutant of fungus. Mycelial growth rate of the white color mutant was relatively better than the other isolates on media added with Cr, Pb, Cu, or Mn, respectly. Tolerance of the white color mutans to heavy metals was higher than that of the black color mutant. It is suggested that tolerance of the white color mutant to heavy metals was not controled by color-related substance of the fungus.

• Journal of Korea Soil Environment Society
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• v.4 no.1
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• pp.35-47
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• 1999

Mine tailings, soils. stream sediments around Gubong disused mine were analyzed in order to investigate their distribution and pollution levels of heavy metals and cyanide. The average contents of As, Cd, Cu. Hg, Pb, Zn, and CN￣ in mine tailings were 6.93$\times$$10^{3}$, 56.9, 209, 5.03, 3.25$\times$$10^{3}$, 1.89$\times$$10^{3}$, 21mg/kg respectively. The pollution indices that calculated by the tolerance level of Kloke were 42~95 and the pH values were slightly alkaline in mine tailings. The contents of heavy metals and cyanide in field soils near the mine were higher than the paddy soils. The contents of heavy metals in the stream sediment were up to that of the tailings, so contamination from the mine tailings were serious.