• BMB Reports
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• 제50권1호
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• pp.49-54
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• 2017

Previously, we reported that vitamin C facilitates the CpG demethylation of Foxp3 enhancer in $CD4^+Foxp3^+$ regulatory T cells (Tregs) by enhancing the activity of a DNA demethylase ten-eleven-translocation (Tet). However, it is not clear whether vitamin C affects other helper T cell lineages like T helper type 17 (Th17) cells which are related with Tregs. Here, we show that the expression of interleukin-17A (IL17) increases with the treatment of vitamin C but not with other antioxidants. Interestingly, the upregulation of IL17 was not accompanied by DNA demethylation in Il17 promoter and was independent of Tet enzymes. Rather, vitamin C reduced the trimethylation of histone H3 lysine 9 (H3K9me3) in the regulatory elements of the Il17 locus, and the effects of vitamin C were abrogated by knockdown of jumonji-C domain-containing protein 2 (jmjd2). These results suggest that vitamin C can affect the expression of IL17 by modulating the histone demethylase activity.

• Journal of Periodontal and Implant Science
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• 제40권4호
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• pp.153-163
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• 2010

Periodontal disease, as a polymicrobial disease, is globally endemic as well as being a global epidemic. It is the leading cause for tooth loss in the adult population and has been positively related to life-threatening systemic diseases such as atherosclerosis and diabetes. As a result, it is clear that more sophisticated therapeutic modalities need to be developed, which may include vaccines. Up to now, however, no periodontal vaccine trial has been successful in satisfying all the requirements; to prevent the colonization of a multiple pathogenic biofilm in the subgingival area, to elicit a high level of effector molecules such as immunoglobulin sufficient to opsonize and phagocytose the invading organisms, to suppress the induced alveolar bone loss, or to stimulate helper T-cell polarization that exerts cytokine functions optimal for protection against bacteria and tissue destruction. This article reviews all the vaccine trials so as to construct a more sophisticated strategy which may be relevant in the future. As an innovative strategy to circumvent these barriers, vaccine trials to stimulate antigen-specific T-cells polarized toward helper T-cells with a regulatory phenotype (Tregs, $CD_{4+}$, $CD_{25+}$, $FoxP_{3+}$) have also been introduced. Targeting not only a single pathogen, but polymicrobial organisms, and targeting not only periodontal disease, but also periodontal disease-triggered systemic disease could be a feasible goal.

• 약학회지
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• 제56권5호
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• pp.326-332
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• 2012

Mast cells play pivotal pathologic roles in allergic disease involving T helper 2 (Th2) cytokine such as interleukin (IL)-4 and IL-13. Fisetin has been known as an anti-allergic agent having inhibitory effects on the IL-4 and IL-13 gene expressions in inflammatory immune cells. However, its molecular mechanisms for suppressive effects of fisetin on IL-4 and IL-13 in activated mast cells have been incompletely elucidated. In this study we found that fisetin significantly inhibited the phorbol 12-myristate 13-acetate (PMA) and ionomycin (PI)-induced production of IL-4 and IL-13 in mast cells. The levels of mRNA were dramatically decreased by fisetin, indicating the suppression might be regulated at the transcriptional levels. Western blot analysis of the nuclear expression of various transcription factors involved in the promoter activation indicated that suppression of c-Fos was prominent together with significant down-regulation of nuclear factor of activated T-cell (NF-AT) and NF-${\kappa}B$, but not c-Jun. Furthermore, the nuclear expression of GATA binding protein 2 (GATA-2) transcription factor was significantly down-regulated by fisetin. Taken together, our study indicated fisetin has suppressive effects on IL-4 and IL-13 gene expression through the regulation of selective transcription factors.

• 대한간호학회지
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• 제41권3호
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• pp.285-293
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• 2011

Purpose: In this study, the effects of laughter therapy on levels of depression, quality of life, resilience and immune responses in breast cancer survivors were examined. Methods: A quasi-experimental nonequivalent control group, pretest-posttest design was used. Participants (n=37) included breast cancer survivors who finished chemotheraphy and radiation therapy: 16 in the experiment group and 21 in the control group. Data were collected from August to November 2009. The experimental group participated in laughter therapy eight times, twice a week for 60 min per session. Questionnaires were used to me-asure pretest and posttest levels of depression, quality of life and resilience. A blood test was used to analyze changes in Total T cell, T helper, T suppressor, Th/Ts ratio, Total B cell, T cell/B cell ratio and NK cell for immune responses. Results: The results showed that laughter therapy was effective in increasing the quality of life and resilience in breast cancer survivors. but depression and immune responses did not differ significantly between the groups. Conclusion: The results of the study indicate that laughter therapy may be an effective nursing intervention to improve quality of life and resilience in breast cancer survivors.

• Journal of Nutrition and Health
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• 제28권10호
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• pp.1004-1014
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• 1995

Effect of age and dietary fatty acid composition on immune responses were investigated in Sprague-Dawley male rets. The animals weighing 88.6$\pm$2.2g were fed 10% dietary fat (W/W, 20% of calorie) with P/S ratio of 0.5, 1 and 2, and in each group, there were three different levels of n-6/n-3 fatty acid ratio; 2, 4 and 8(3$\times$3). The experimental periods were 1 month, 6 months and 12 months. The results of this study were; 1) Weights of thymus and spleen were significantly reduced with increasing age, moreover thymus weights were reduced with increasing the degree of unsaturation in dietarty fatty acid at 12 month. 2) The proportion of splenic lymphocyte in the total T-cell was increased with increased with age. The proportion of helper T-cell was not changed, while the proportion of suppressor T-cell was decreased. Thus at 12 month, the ratio of helpe $r^pressor T-cell was appeared to increase significantly, and showed the tendency to increase by consuming the low amount of dieraty n-3 fatty acid. 3) Proliferation stimulated by Con A or PWM reduced significantly at 12 month in which are high in dietary P/S ratio, representing the similar pattern with decrease in thymus weight. 4) Natural killer cell activities were shown significantly higher at 1 month than those at 6 month or 12 month.th.

• International Journal of Oral Biology
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• 제38권1호
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• pp.37-42
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• 2013

Receptor activator of NF-${\kappa}B$ ligand (RANKL) is an essential cytokine for osteoclast differentiation, activation and survival. T lymphocytes such as $T_{17}$ cells, a subset of T helper cells that produce IL-17, play an important role in rheumatoid arthritic bone resorption by producing inflammatory cytokines and RANKL. It has not yet been clearly elucidated how T cell activation induces RANKL expression. T cell receptor activation induces the activation of nuclear factor of activated T cell (NFAT) and expression of its target genes. In this study, we examined the role of NFAT in T cell activation-induced RANKL expression. EL-4, a murine T lymphocytic cell line, was used. When T cell activation was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin, RANKL expression increased in a time-dependent manner. In the presence of cyclosporin, an inhibitor of NFAT activation, this PMA/ionomycin-induced RANKL expression was blocked. Overexpression of either NFATc1 or NFATc3 induced RANKL expression. Chromatin immunoprecipitation results demonstrated that PMA/ionomycin treatment induced the binding of NFATc1 and NFATc3 to the mouse RANKL gene promoter. These results suggest that NFATc1 and NFATc3 mediates T cell receptor activation-induced RANKL expression in T lymphocytes.

• IMMUNE NETWORK
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• 제1권3호
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• pp.236-243
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• 2001

Background: An immunological approach for aging mechanism appears to be important. Lymphocyte subsets analysis in peripheral blood is widely performed to assess the immune status and to diagnose and monitor various diseases. Some lymphocyte subsets are known to change with age, but only few data about age-related reference ragnes for these subsets in healthy individuals have been reported. So we attempted to report reference ranges for these subsets in each age group and review changes of the results with age for the secondary studies about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement (VDJ) including recombination activating genes (RAG-1 and RAG-2). Methods: Lymphocyte subset analysis was performed on 302 subjects, 189 males and 113 females with age group of all decades of life. Two color direct immunofluorescene flow cytometry (FCM) was done using $Simultest^{TM}$ IMK-Lymphocyte kit (Becton Dickinson, USA), $FACScan^{TM}$ (Becton Dickinson, USA) and $FACSCalibur^{TM}$ (Becton Dickinson, USA). Lymphocyte subsets analysed were T ($CD3^+$) and B cells ($CD19^+$), helper/inducer T ($CD4^+$) and suppressor/cytotoxic T cells ($CD8^+$), helper/suppressor ($CD4^+/CD8^+$) ratio and natural killer (NK) cells ($CD3^-CD16^+/CD56^+$). The absolute numbers of each subset were calculated from total lymphocyte counts. Data collected was analysed using SAS 6.12. A P-value of < 0.05 was considered significant. Results: We reported the counts and percentages of lymphocyte and these subsets in each age group. There were no statistically significant differences between male and female subjects. The percentage of $CD4^+$ T cells, and the count of NK cells did not show the significant difference among the various age groups. The age-related changes observed in our study were as following: 1) a decrease in the percentages of T cells, B cells and $CD8^+$ T cells ; 2) a decrease in the counts of B cells and $CD8^+$ T cells ; 3) an increase in the percentage and count of NK cells ; and 4) an increase in the $CD4^+/CD8^+$ ratio. Conclusion: The characteristics of aging process appeared to be showing a marked decrease of lympocyte subsets T and B cells as well as T8 ($CD8^+$). The age-related increase of the percentage of cells bearing NK marker can be interpreted as a compensatory consequence to cope with the decrease of T cells related to the thymic involution. These changes with age appeared to be for the secondary study about immune cell function as lymphocyte blast transformation and immunoglobulin gene rearrangement.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.244-251
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• 2016

Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of $TGF-{\beta}$. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

• 미생물과산업
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• 제16권3호
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• pp.20-25
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• 1990

면역계에는 조력T세포(helper T cell)와는 반대로 면역반응을 억제적으로 조절하는 것이 주 기능인 억제성 T세포(suppressor T cell)가 존배한다는 것이 아려져 있다. 이 억제성 T세포가 존재한다는 개념이 면역학및 임상의학에 준 영향은 매우 지대하여, 앨러지나 자가 면역질환 같은 질병은 억제성 T세포의 결핍으로, 그리고 면역 결핍증같은 질병은 T세포가 지나치게 활성화된 것으로 설명되기에 이르렀다. 한마디로 거의 모든 저하된 면역반응은 억제성 T세포와 연관하여 설명되었다. 그러나 억제성 T세포가 발견된지 근 20년이 되고 그에 관한 논문이 5000여편에 달하는 최근까지도 억제성 T세포 및 이들 세포가 만드는 억제성 T세포 인자에 대한 실체는 정확히 규명되지 못하고 있다. 오히려 억제성 T세포가 조력 T세포처럼 별개의 세포군으로 존재한다는 것을 부인하는 학자도 최근 나오게 되었다.(이 분야의 연구에서 나타난 문제점들이 정리되어 있음). 그러나 억제성 T세포의 존재를 부인하는 학자들도 T세포가 면역 반응의 억제에 관여한다는 사실, 적어도 그 현상 자체를 부인하지는 않았다. 다시말하면, 면역반응이 T세포에 의하여 억제되는 현상은 이미 수 천년의 논문을 통하여 입증되고 있다. 면역반응의 억제에 있어서 억제성 T세포및 억제성 T세포 인자의 역할은 앞으로의 연구를 통해 명확히 규명될 것이며, 정말 억제성 T세포가 있느냐 없느냐 하는 것은 이 총설의 주제가 아니다. 다만 여기서는 조력 T세포도 경우에 따라서는 면역반응의 억제에 관여한다는 최근의 연구결과를 간단히 소개하고자 한다.

• Journal of Ginseng Research
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• 제40권1호
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• pp.18-27
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• 2016

Background: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. Methods: Using CD4+ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naïve T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. Results: Under TCR stimulation, KRGE treatment did not affect the population of CD4+interferon gamma ($IFN{\gamma}$)+ and CD4+interleukin (IL)-4+ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4+IL-17+ cells and CD4+/phosphorylated STAT3 (p-STAT3)+ cells, but increased the number of CD4+CD25+forkhead box P3 (Foxp3)+ cells and CD4+/p-STAT5+ cells compared with CsA alone. In allogeneic APCs-stimulated CD4+ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4+IL-17+ cells and increased the number of CD4+CD25+Foxp3+ cells under the Th17-polarizing condition. Conclusion: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression.