• IMMUNE NETWORK
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• v.22 no.1
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• pp.9.1-9.23
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• 2022

In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, and intracellular kinases have become the standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, and IL-23 has revolutionized the treatment of autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriasis. B cell depletion therapy using anti-CD20 mAbs has shown promising results in patients with neuroinflammatory diseases, and inhibition of B cell survival factors is approved for treatment of systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells and T cells is also expected to have therapeutic potential in autoimmune diseases by modulating T cell function. Recently, small molecule kinase inhibitors targeting the JAK family, which is responsible for signal transduction from multiple receptors, have garnered great interest in the field of autoimmune and hematologic diseases. However, there are still unmet medical needs in terms of therapeutic efficacy and safety profiles. Emerging therapies aim to induce immune tolerance without compromising immune function, using advanced molecular engineering techniques.

• IMMUNE NETWORK
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• v.19 no.1
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• pp.6.1-6.14
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• 2019

Plasmacytoid dendritic cells (pDCs) are a unique subset of cells with different functional characteristics compared to classical dendritic cells. The pDCs are critical for the production of type I IFN in response to microbial and self-nucleic acids. They have an important role for host defense against viral pathogen infections. In addition, pDCs have been well studied as a critical player for breaking tolerance to self-nucleic acids that induce autoimmune disorders such as systemic lupus erythematosus. However, pDCs have an immunoregulatory role in inducing the immune tolerance by generating Tregs and various regulatory mechanisms in mucosal tissues. Here, we summarize the recent studies of pDCs that focused on the functional characteristics of gut pDCs, including interactions with other immune cells in the gut. Furthermore, the dynamic role of gut pDCs will be investigated with respect to disease status including gut infection, inflammatory bowel disease, and cancers.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.17 no.2
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• pp.98-103
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• 2014

Purpose: Gallbladder (GB) wall thickening can be found in various conditions unrelated to intrinsic GB disease. We investigated the predisposing etiologies and the outcome of acalculous GB wall thickening in children. Methods: We retrospectively analyzed 67 children with acalculous GB wall thickening who had visited our institute from June 2010 to June 2013. GB wall thickening was defined as a GB wall diameter > 3.5 mm on abdominal ultrasound examination or computed tomography. Underlying diseases associated with GB wall thickening, treatment, and outcomes were studied. Results: There were 36 boys and 31 girls (mean age, $8.5{\pm}4.8years$ [range, 7 months-16 years]). Systemic infection in 24 patients (35.8%), acute hepatitis in 18 (26.9%), systemic disease in 11 (16.4%), hemophagocytic lymphohistiocytosis in 4 (6.0%), acute pancreatitis in 3 (4.5%), and specific liver disease in 3 (4.5%) predisposed patients to GB wall thickening. Systemic infections were caused by bacteria in 10 patients (41.7%), viruses in 5 patients (20.8%), and fungi in 2 patients (8.3%). Systemic diseases observed were systemic lupus erythematosus in 2, drug-induced hypersensitivity in 2, congestive heart failure in 2, renal disorder in 2. Sixty-one patients (91.0%) received symptomatic treatments or treatment for underlying diseases. Five patients (7.5%) died from underlying diseases. Cholecystectomy was performed in 3 patients during treatment of the underlying disease. Conclusion: A wide range of extracholecystic conditions cause diffuse GB wall thickening that resolves spontaneously or with treatment of underlying diseases. Surgical treatments should be avoided if there are no definite clinical manifestations of cholecystitis.

• IMMUNE NETWORK
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• v.4 no.3
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• pp.161-165
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• 2004

Background: Anti-cardiolipin antibody (Anti-CL Ab) is one of the various antiphospholipid antibodies (Anti-PL Abs) and found in the plasma of patients with systemic lupus erythematosus (SLE), atherosclerosis, and other infectious diseases. While anti-PL Abs found in the sera of patients with infectious diseases bind directly to CL, binding of anti-PL Abs to CL circulating in the sera of patients with autoimmune diseases is mediated by $\beta_2-$glycoprotein 1 ($\beta_2-GP1$). The purpose of this study is to investigate the effect of <$\beta_2-GP1$ on the antigen binding assay of anti-CL Abs present in the sera of patients with atherosclerosis, which has been known as one of autoimmune diseases. Methods: ELISA was performed with sera containing anti-CL Abs from three patients with atherosclerosis in the presence or absence of $\beta_2-GP1$ or FBS. Results: Reactivity of anti-CL Abs to CL was increased in the presence of $\beta_2-GP1$ or FBS in a dose dependent manner. Conclusion: <$\beta_2-GP1$ or FBS could be used as co-factor in CL ELISA with anti-CL Abs present in the sera of patients with atherosclerosis. It is suggested that anti-CL Abs found in atherosclerosis patients are similar in terms of antigen binding property to those circulating in the patients with autoimmune diseases, not to infectious diseases.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.10-17
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• 2007

Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

• Journal of Forest and Environmental Science
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• v.35 no.4
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• pp.281-284
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• 2019

Efficient management of road-kill data is difficult at national scale when there are many organizations that are in charge of different road types. Here, we described the first case to integrate road-kill data through Korea Road-kill Observation System (KROS) by the Korean government. The system was launched in June 2018 to approximately 3,000 road menders. During 15 months, 5,812 road-kill observations were registered on KROS including mammals, birds, reptiles and amphibians. Of them, about 86 % was occupied by five species (Hydropotes inermis, Felis catus, Capreolus pygargus, Nyctereutes procyonoides, and Canis lupus familiaris) listed in number of occurrences. The observed road-kill frequency rapidly increased until April 2019 and peaked on May 2019. However, as the system is just starting, the results from KROS cannot be treated as the exact representation of road-kill trend in the country. Although the efficient method to manage national road-kill statistic is arranged, still there are some limitations to overcome to make the system stable.

• Tuberculosis and Respiratory Diseases
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• v.67 no.4
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• pp.351-355
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• 2009

The incidence of pulmonary thromboembolism increases with age. The risk factors of pulmonary thromboembolism include surgery, malignancy, obesity, lupus anticoagulants, and vascular conditions such as deep vein thrombosis. Thromboembolism in younger patients or in unusual locations, the possibility of primary thrombophilic conditions should be considered. Primary thrombophilic states include myeloproliferative disorders (MPD). JAK2 V617F mutation is found commonly in patients diagnosed with MPD, in 90~95% of polycythemia vera (PV) and in 50~60% of essential thrombocytosis (ET) patients. Sometimes the JAK2 V617F mutation is found in cases without MPD. The relationship between JAK2 V617F mutation and thrombosis has not been defined. Recently, clinical evidence suggests that this mutation may be variably associated with thrombosis. We present one case of pulmonary thromboembolism in a young patient, who was positive for the JAK2 V617F mutation and did not have MPD.

• Preventive Nutrition and Food Science
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• v.15 no.1
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• pp.14-18
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• 2010

Stevia rebaudiana (SR) is an herb used traditionally as a sweetener in Paraguay and Brazil, whose use is spreading to other countries, such as Japan, Korea and China. In addition to its low calorie sweet taste, SR appears to have other beneficial properties, such as hypotensive capabilities and inflammation reduction. To identify the bioactive natural constituents exerting anti-inflammatory activities, we examined the EtOAc fraction of SR. In the inflammatory mediator inhibitory assay from lipopolysaccharide (LPS)-activated macrophages, the EtOAc fraction significantly, and dose dependently, inhibited the enhanced production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression. We also found that treatment of cells with the EtOAc fraction significantly inhibited LPS-stimulated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) reporter gene expression. Such inhibition of NF-${\kappa}B$ was closely associated with the inhibition of interleukin-6 (IL-6) and the monocyte chemoattractant protein-1 (MCP-1). Therefore, we suggest that SR has the potential for development as a functional food for the treatment of immune diseases, such as rheumatoid arthritis and lupus.

• Childhood Kidney Diseases
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• v.10 no.2
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• pp.174-181
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• 2006

Purpose : To analyse the results of the renal biopsies and the clinical diagnoses of patients who had undergone percutaneous kidney biopsies in the department of pediatrics at Kyunghee University Hospital for 22 years from 1984 to 2005. Methods : We retrospectively reviewed the medical records of 1559 patients and analyzed the chief complaints that led to a renal biopsy, age, sex, histopathologic findings and diagnosis. Routine kidney biopsies were performed by automated gun biopsy guided by real time ultrasonography. The diagnoses were made based on the specimen's light microscopy, immunofluorescence microscopy and electron microscopy findings and clinical symptoms and signs. Results : The mean age of the patients was 10 years with the male to female ratio being 1.3:1. The chief complaints that led to a renal biopsy included hematuria only(753 cases, 48.3%), proteinuria only(125 cases, 8.0%) and hematuria combined with proteinuria(537 cases, 34.4%). The most frequent histopathological finding was primary glomerular disease(75.4%) which included IgA nephropathy(30.1%) and mesangial proliferative glomerulonephritis(27.6 %). Systemic disease comprised 11.4% which included Henoch-$Sch\ddot{o}nlein$ nephritis(10.5%) and lupus nephritis(0.8%). Alport syndrome was found in 1.1% of cases which was attributed to hereditary causes. 628 children(40.3%) visited the clinic due to abnormal school urine screening abnormalities and among these, 237 children had mesangial proliferative glomerulonephritis and 234 children who had IgA nephropathy were managed thereafter. Conclusion : IgA nephropathy and mesangial proliferative glomerulonephritis were the two major forms of primary glomerulonephritis found in Korean children who had kidney biopsies from 1984 to 2005.