• Genomics & Informatics
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• v.13 no.4
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• pp.126-131
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• 2015

Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The $HLA-DRB1^*04:05-HLA-DQB1^*04:01$ haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009). A histidine residue at $HLA-DR{\beta}1$ position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI, 1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.

• IMMUNE NETWORK
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• v.14 no.3
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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.

• Molecules and Cells
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• v.40 no.5
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• pp.355-362
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• 2017

The ${\beta}2$ integrins are cell surface transmembrane proteins regulating leukocyte functions, such as adhesion and migration. Two members of ${\beta}2$ integrin, ${\alpha}M{\beta}2$ and ${\alpha}X{\beta}2$, share the leukocyte distribution profile and integrin ${\alpha}X{\beta}2$ is involved in antigen presentation in dendritic cells and transendothelial migration of monocytes and macrophages to atherosclerotic lesions. ${\underline{R}}eceptor$ for ${\underline{a}}dvanced$ ${\underline{g}}lycation$ ${\underline{e}}nd$ ${\underline{p}}roducts$ (RAGE), a member of cell adhesion molecules, plays an important role in chronic inflammation and atherosclerosis. Although RAGE and ${\alpha}X{\beta}2$ play an important role in inflammatory response and the pathogenesis of atherosclerosis, the nature of their interaction and structure involved in the binding remain poorly defined. In this study, using I-domain as a ligand binding motif of ${\alpha}X{\beta}2$, we characterize the binding nature and the interacting moieties of ${\alpha}X$ I-domain and RAGE. Their binding requires divalent cations ($Mg^{2+}$ and $Mn^{2+}$) and shows an affinity on the sub-micro molar level: the dissociation constant of ${\alpha}X$ I-domains binding to RAGE being $0.49{\mu}M$. Furthermore, the ${\alpha}X$ I-domains recognize the V-domain, but not the C1 and C2-domains of RAGE. The acidic amino acid substitutions on the ligand binding site of ${\alpha}X$ I-domain significantly reduce the I-domain binding activity to soluble RAGE and the alanine substitutions of basic amino acids on the flat surface of the V-domain prevent the V-domain binding to ${\alpha}X$ I-domain. In conclusion, the main mechanism of ${\alpha}X$ I-domain binding to RAGE is a charge interaction, in which the acidic moieties of ${\alpha}X$ I-domains, including E244, and D249, recognize the basic residues on the RAGE V-domain encompassing K39, K43, K44, R104, and K107.

• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.302-310
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• 2019

Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and -resistant (A375P/Mdr with acquired resistance and SK-MEL-2 with intrinsic resistance) melanoma cell lines, to reveal the genes and pathways potentially involved in intrinsic and acquired resistance to BRAF inhibitors. A total of 546 differentially expressed genes (DEGs), including 239 up-regulated and 307 down-regulated genes, were identified in both intrinsic and acquired resistant cells. Gene ontology (GO) analysis revealed that the top 10 biological processes associated with these genes included angiogenesis, immune response, cell adhesion, antigen processing and presentation, extracellular matrix organization, osteoblast differentiation, collagen catabolic process, viral entry into host cell, cell migration, and positive regulation of protein kinase B signaling. In addition, using the PAN-THER GO classification system, we showed that the highest enriched GOs targeted by the 546 DEGs were responses to cellular processes (ontology: biological process), binding (ontology: molecular function), and cell subcellular localization (ontology: cellular component). Ingenuity pathway analysis (IPA) network analysis showed a network that was common to two BRAF inhibitorresistant cells. Taken together, the present study may provide a useful platform to further reveal biological processes associated with BRAF inhibitor resistance, and present areas for therapeutic tool development to overcome BRAF inhibitor resistance.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.3
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• pp.307-313
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• 2015

The present study investigated the immunomodulatory effects of Curcuma longa L. ethanol extracts on natural killer (NK) cells and T cells. We treated Curcuma longa L. ethanol extracts at concentrations of 20, 50, 100, and $150{\mu}g/mL$ to murine NK cells co-incubated with YAC-1 cells. Curcuma longa L. ethanol extracts resulted in increased NK cell activity compared to the control group at all concentrations. In the groups treated with Curcuma longa L. ethanol extracts, CD69 and IFN-${\gamma}$ expression levels significantly increased compared to the control group at 100 and $150{\mu}g/mL$. In addition, Curcuma longa L. ethanol extracts induced significant elevation of CD8+ T cell numbers in a dose-dependent manner. However, Curcuma longa L. ethanol extracts also led to reduction of CD4+ T cell and MHCII numbers. The findings of this study suggest that Curcuma longa L. ethanol extracts could enhance the immune response through activation of NK and cytotoxic T cells due to a proliferative shift of antigen presentation from MHCII to MHCI, presumably.

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1166-1171
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• 2007

Exercise is the strongest stress to which the body is ever exposed. The body responds to this stress through a set of physiological changes in its metabolic, hormonal, and immunological systems. In this study, responses of the immune system to the long-term aerobic and anaerobic exercises have been investigated. Regular moderate exercise is associated with a reduced incidence of infection compared with a sedentary groups. Aerobic training increases the heart rate and enhances the body's intake of oxygen long enough to benefit the condition of the body. In recent years, the importance of exercise in everyday life has been rapidly increasing. Moderate exercise appears to stimulate the immune system. And also, Exercise elicits an increase in the numbers of circulating lymphocytes and lymphocyte subsets (including NK cells) which is followed by a decrease in the numbers of cells during recovery from exercise. However, prolonged bouts of strenuous exercise cause a temporary depression of various aspects of immune functions (e.g. lymphocyte proliferation, monocyte antigen presentation, open window periods, exercise induced asthma, exercise induced anaphylaxis) that usually lasts 2-24 hr after exercise depending on the intensity and duration of the exercise bout. Exercise-induced bronchoconstriction (EIB) was defined as a decrease of at least 15% in pre exercise forced expiratory volume in one second at any time point after exercise. This includes elevation of cortisol and cathecholamines in plasma. On the other hand, highly trained athletes exhibit a chronic mild hypercortisolism at baseline that maybe an adaptive change to chronic exercise. And, Consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression. Recent evidence suggests that antioxidant vitamin supplementation may also reduce exercise stress and impairment of leukocyte functions.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.9
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• pp.1507-1519
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• 2020

Objective: The current research was aimed to profile the transcriptomic picture of the peripheral blood lymphocytes (PBLs) associated with immunity in Chinese Holsteins supplemented orally with coated folic acid during the periparturient period. Methods: The total of 123 perinatal cows were selected for this study and divided into three groups; group A (n = 41, 240 mg/500 kg cow/d), group B (n = 40, 120 mg/500 kg cow/d) and group C (n = 42, 0 mg/cow/d) based on the quantity of folic acid fed. Three samples of PBLs were selected from each folic acid treated group (high, low, and control) and RNA sequencing method was carried out for transcriptomic analysis. Results: The analysis revealed that a higher number of genes and pathways were regulated in response to high and low folic acid supplementation compared to the controls. We reported the novel pathways tumor necrosis factor (TNF) signaling, antigen processing and presentation, Staphylococcus aureus infection and nuclear factor (NF)-kappa B signaling pathways) and the key genes (e.g. C-X-C motif chemokine ligand 10, TNF receptor superfamily member 1A, cluster difference 4, major histocompatibility complex, class II, DQ beta, NF-kappa-B inhibitor alpha, and TNF superfamily 13) having great importance in immunity and anti-inflammation in the periparturient cows in response to coated folic acid treatment. Conclusion: Collectively, our study profiled first-time transcriptomic analysis of bovine lymphocytes and compared the involved cytokines, genes, and pathways between high vs control and low vs control. Our data suggest that the low folic acid supplementation (120 mg/500 kg) could be a good choice to boost appropriate immunity and anti-inflammation as well as might being applied to the health improvement of perinatal dairy cows.

• Tuberculosis and Respiratory Diseases
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• v.68 no.2
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• pp.74-79
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• 2010

Background: Legionella pneumophila has been recognized as an important cause of pneumonia. However, limited data are available in the literature regarding legionella pneumonia in Korea. The objective of this study was to compare epidemiological data and clinical presentation of legionella pneumonia and pneumococcal pneumonia. Methods: We retrospectively compared clinical, radiological, and laboratory data, antimicrobial treatment, and treatment outcomes between 28 cases of legionella pneumonia and 56 cases of pneumococcal pneumonia. Diagnoses of both legionella and pneumococcal pneumonia were based on commercial urinary antigen tests. Results: Legionella pneumonia patients included 23 men and 5 women, with a mean age of 61.6 years (range 36~88). Fifteen were smokers and 26 had some underlying diseases. Legionella pneumonia occurred more frequently in healthcare-associated settings than pneumococcal pneumonia (42.9% vs 21.4%, respectively, p=0.040). There were no significant differences in clinical signs and symptoms. Compared to patients with pneumococcal pneumonia, patients with legionella pneumonia presented more frequently with anemia (39.3% vs 8.9%, p=0.001), increased C-reactive protein (57.1% vs 30.4%, p=0.018) and increased alkaline phosphatase (46.4% vs 16.1%, p=0.003). Also, legionella pneumonia patients more often showed pleural effusion on simple chest X-rays (50.0% vs 12.5%, p<0.001). Conclusion: Legionella pneumonia and pneumococcal pneumonia can not be distinguished by clinical manifestations alone. However, legionella pneumonia occurred as a healthcare-associated pneumonia more frequently and was more often associated with anemia and increased CRP and alkaline phosphatase levels.

• Journal of Veterinary Science
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• v.23 no.1
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• pp.2.1-2.18
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• 2022

Background: Co-infections of the porcine reproductive and respiratory syndrome virus (PRRSV) and the Haemophilus parasuis (HPS) are severe in Chinese pigs, but the immune response genes against co-infected with 2 pathogens in the lungs have not been reported. Objectives: To understand the effect of PRRSV and/or HPS infection on the genes expression associated with lung immune function. Methods: The expression of the immune-related genes was analyzed using RNA-sequencing and bioinformatics. Differentially expressed genes (DEGs) were detected and identified by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and western blotting assays. Results: All experimental pigs showed clinical symptoms and lung lesions. RNA-seq analysis showed that 922 DEGs in co-challenged pigs were more than in the HPS group (709 DEGs) and the PRRSV group (676 DEGs). Eleven DEGs validated by qRT-PCR were consistent with the RNA sequencing results. Eleven common Kyoto Encyclopedia of Genes and Genomes pathways related to infection and immune were found in single-infected and co-challenged pigs, including autophagy, cytokine-cytokine receptor interaction, and antigen processing and presentation, involving different DEGs. A model of immune response to infection with PRRSV and HPS was predicted among the DEGs in the co-challenged pigs. Dual oxidase 1 (DUOX1) and interleukin-21 (IL21) were detected by IHC and western blot and showed significant differences between the co-challenged pigs and the controls. Conclusions: These findings elucidated the transcriptome changes in the lungs after PRRSV and/or HPS infections, providing ideas for further study to inhibit ROS production and promote pulmonary fibrosis caused by co-challenging with PRRSV and HPS.

• Korean Journal of Radiology
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• v.24 no.11
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• pp.1102-1113
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• 2023

Objective: To elucidate the use of radiological studies, including nuclear medicine, and biopsy for the diagnosis and staging of prostate cancer (PCA) in clinical practice and understand the current status of PCA in Asian countries via an international survey. Materials and Methods: The Asian Prostate Imaging Working Group designed a survey questionnaire with four domains focused on prostate magnetic resonance imaging (MRI), other prostate imaging, prostate biopsy, and PCA backgrounds. The questionnaire was sent to 111 members of professional affiliations in Korea, Japan, Singapore, and Taiwan who were representatives of their working hospitals, and their responses were analyzed. Results: This survey had a response rate of 97.3% (108/111). The rates of using 3T scanners, antispasmodic agents, laxative drugs, and prostate imaging-reporting and data system reporting for prostate MRI were 21.6%-78.9%, 22.2%-84.2%, 2.3%-26.3%, and 59.5%-100%, respectively. Respondents reported using the highest b-values of 800-2000 sec/mm² and fields of view of 9-30 cm. The prostate MRI examinations per month ranged from 1 to 600, and they were most commonly indicated for biopsy-naïve patients suspected of PCA in Japan and Singapore and staging of proven PCA in Korea and Taiwan. The most commonly used radiotracers for prostate positron emission tomography are prostate-specific membrane antigen in Singapore and fluorodeoxyglucose in three other countries. The most common timing for prostate MRI was before biopsy (29.9%). Prostate-targeted biopsies were performed in 63.8% of hospitals, usually by MRI-ultrasound fusion approach. The most common presentation was localized PCA in all four countries, and it was usually treated with radical prostatectomy. Conclusion: This survey showed the diverse technical details and the availability of imaging and biopsy in the evaluation of PCA. This suggests the need for an educational program for Asian radiologists to promote standardized evidence-based imaging approaches for the diagnosis and staging of PCA.