• IMMUNE NETWORK
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• 제22권2호
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• pp.14.1-14.17
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• 2022

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.

• IMMUNE NETWORK
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• 제20권5호
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• pp.38.1-38.12
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• 2020

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that initiate both T-cell responses and tolerance. Tolerogenic DCs (tDCs) are regulatory DCs that suppress immune responses through the induction of T-cell anergy and Tregs. Because lactoferrin (LF) was demonstrated to induce functional Tregs and has a protective effect against inflammatory bowel disease, we explored the tolerogenic effects of LF on mouse bone marrow-derived DCs (BMDCs). The expression of CD80/86 and MHC class II was diminished in LF-treated BMDCs (LF-BMDCs). LF facilitated BMDCs to suppress proliferation and elevate Foxp3⁺ induced Treg (iTreg) differentiation in ovalbumin-specific CD4⁺ T-cell culture. Foxp3 expression was further increased by blockade of the B7 molecule using CTLA4-Ig but was diminished by additional CD28 stimulation using anti-CD28 Ab. On the other hand, the levels of arginase-1 and indoleamine 2,3-dioxygenase-1 (known as key T-cell suppressive molecules) were increased in LF-BMDCs. Consistently, the suppressive activity of LF-BMDCs was partially restored by inhibitors of these molecules. Collectively, these results suggest that LF effectively causes DCs to be tolerogenic by both the suppression of T-cell proliferation and enhancement of iTreg differentiation. This tolerogenic effect of LF is due to the reduction of costimulatory molecules and enhancement of suppressive molecules.

• IMMUNE NETWORK
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• 제20권5호
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• pp.39.1-39.13
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• 2020

Sjögren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. In SS, type I IFN has a pathogenic role, and recently, inflammasome activation has been observed in both immune and non-immune cells. However, the relationship between type I IFN and inflammasome-associated pyroptosis in SS has not been studied. We measured IL-18, caspase-1, and IFN-stimulated gene 15 (ISG15) in saliva and serum, and compared whether the expression levels of inflammasome and pyroptosis components, including absent in melanoma 2 (AIM2), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and gasdermin E (GSDME), in minor salivary gland (MSG) are related to the expression levels of type I IFN signature genes. Expression of type I IFN signature genes was correlated with mRNA levels of caspase-1 and GSDMD in MSG. In confocal analysis, the expression of caspase-1 and GSDMD was higher in salivary gland epithelial cells (SGECs) from SS patients. In the type I IFN-treated human salivary gland epithelial cell line, the expression of caspase-1 and GSDMD was increased, and pyroptosis was accelerated in a caspase-dependent manner upon inflammasome activation. In conclusion, we demonstrate that type I IFN may contribute to inflammasome-associated pyroptosis of the SGECs of SS patients, suggesting another pathogenic role of type I IFN in SS in terms of target tissue -SGECs destruction.

• IMMUNE NETWORK
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• 제16권4호
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• pp.242-248
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• 2016

Thymic atrophy is a complication that results from exposure to many environmental stressors, disease treatments, and microbial challenges. Such acute stress-associated thymic loss can have a dramatic impact on the host's ability to replenish the necessary naïve T cell output to reconstitute the peripheral T cell numbers and repertoire to respond to new antigenic challenges. We have previously reported that treatment with the orexigenic hormone ghrelin results in an increase in the number and proliferation of thymocytes after dexamethasone challenge, suggesting a role for ghrelin in restraint stress-induced thymic involution and cell apoptosis and its potential use as a thymostimulatory agent. In an effort to understand how ghrelin suppresses thymic T cell apoptosis, we have examined the various signaling pathways induced by receptor-specific ghrelin stimulation using a restraint stress mouse model. In this model, stress-induced apoptosis in thymocytes was effectively blocked by ghrelin. Western blot analysis demonstrated that ghrelin prevents the cleavage of pro-apoptotic proteins such as Bim, Caspase-3, and PARP. In addition, ghrelin stimulation activates the Akt and Mitogen-activated protein kinases (MAPK) signaling pathways in a time/dose-dependent manner. Moreover, we also revealed the involvement of the FoxO3a pathway in the phosphorylation of Akt and ERK1/2. Together, these findings suggest that ghrelin inhibits apoptosis by modulating the stress-induced apoptotic signal pathway in the restraint-induced thymic apoptosis.

• IMMUNE NETWORK
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• 제20권3호
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• pp.27.1-27.11
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• 2020

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9-8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6-2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8-10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

• Clinical Endoscopy
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• 제57권2호
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• pp.141-157
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• 2024

Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.

• IMMUNE NETWORK
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• 제24권3호
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• pp.19.1-19.15
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• 2024

The influenza virus poses a global health burden. Currently, an annual vaccine is used to reduce influenza virus-associated morbidity and mortality. Most influenza vaccines have been developed to elicit neutralizing Abs against influenza virus. These Abs primarily target immunodominant epitopes derived from hemagglutinin (HA) or neuraminidase (NA) of the influenza virus incorporated in vaccines. However, HA and NA are highly variable proteins that are prone to antigenic changes, which can reduce vaccine efficacy. Therefore, it is essential to develop universal vaccines that target immunodominant epitopes derived from conserved regions of the influenza virus, enabling cross-protection among different virus variants. The internal proteins of the influenza virus serve as ideal targets for universal vaccines. These internal proteins are presented by MHC class I molecules on Ag-presenting cells, such as dendritic cells, and recognized by CD8 T cells, which elicit CD8 T cell responses, reducing the likelihood of disease and influenza viral spread by inducing virus-infected cell apoptosis. In this review, we highlight the importance of CD8 T cell-mediated immunity against influenza viruses and that of viral epitopes for developing CD8 T cell-based influenza vaccines.

• IMMUNE NETWORK
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• 제24권3호
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• pp.21.1-21.16
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• 2024

IL-1, a pleiotropic cytokine with profound effects on various cell types, particularly immune cells, plays a pivotal role in immune responses. The proinflammatory nature of IL-1 necessitates stringent control mechanisms of IL-1-mediated signaling at multiple levels, encompassing transcriptional and translational regulation, precursor processing, as well as the involvement of a receptor accessory protein, a decoy receptor, and a receptor antagonist. In T-cell immunity, IL-1 signaling is crucial during both the priming and effector phases of immune reactions. The fine-tuning of IL-1 signaling hinges upon two distinct receptor types; the functional IL-1 receptor (IL-1R) 1 and the decoy IL-1R2, accompanied by ancillary molecules such as the IL-1R accessory protein (IL-1R3) and IL-1R antagonist. IL-1R1 signaling by IL-1β is critical for the differentiation, expansion, and survival of Th17 cells, essential for defense against extracellular bacteria or fungi, yet implicated in autoimmune disease pathogenesis. Recent investigations emphasize the physiological importance of IL-1R2 expression, particularly in its capacity to modulate IL-1-dependent responses within Tregs. The precise regulation of IL-1R signaling is indispensable for orchestrating appropriate immune responses, as unchecked IL-1 signaling has been implicated in inflammatory disorders, including Th17-mediated autoimmunity. This review provides a thorough exploration of the IL-1R signaling complex and its pivotal roles in immune regulation. Additionally, it highlights recent advancements elucidating the mechanisms governing the expression of IL-1R1 and IL-1R2, underscoring their contributions to fine-tuning IL-1 signaling. Finally, the review briefly touches upon therapeutic strategies targeting IL-1R signaling, with potential clinical applications.

• 원예과학기술지
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• 제30권5호
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• pp.557-567
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• 2012

본 연구는 마커이용여교잡(marker-assisted backcross, MAB)을 통한 내병성 토마토 신품종육성에 필요한 기초 정보를 얻기 위해 수행되었다. TYLCV, 시들음역병, 청고병, 흰가루병에 내병성인 공여친 계통 10종과 이병성이지만 우수 원예형질을 지닌 회복친 계통 4종에 대해 병리검정과 TYLCV 내병성 연관 분자마커 분석을 수행하였다. MAB를 위한 회복친 유전자 선발(background selection)용 마커개발을 목표로 SOL Genomics Network에 공시된 토마토 유전자지도(reference map)로부터 전 게놈에 균등히 분포된 108개(염색체 당 평균 9개) SSR 마커를 분석하여, 총 303개의 다형성 마커를 기반으로 공여친, 회복친 계통 간 유연관계를 분석하였다. 그 결과, 유사도 값의 전체 범위는 0.33-0.80으로계통 간 가장 높은 유사도 값(0.80)을 나타낸 것은 청고병에 저항성인 '10BA333'와 '10BA424'이었고, 가장 낮은 유사도 값(0.33)을 나타낸 것은 시들음역병에 내병성인 야생종 L3708(Solanum pimpinelliforium L.)과 청고병에 저항성인 '10BA424'이었다. 유사도 값을 이용하여 UPGMA 분석한 결과, 유사도 0.58를 기준으로 나누었을 때 3개의 군(cluster)으로 분류되었는데, 대부분 동일한 내병성을 지닌 공여친계통 간 유전적 거리가 가까워 이들은 공통된 저항성 재료를 이용한 육성과정에서 파생된 계통일 것이라 판단되었다. 계통수(dendrogram)를 기준으로 유전적 거리가 지나치게 멀지 않으면서 비교적 다수의 회복친 유전자 선발용 SSR 마커의 확보가 가능한 여교배 조합(공여친 ${\times}$ 회복친)은 TYLCV 내병성의 경우 'TYR1' ${\times}$ 'RPL1', 청고병의 경우 '10BA333' 또는 '10BA424' ${\times}$ 'RPL2', 흰가루병의 경우 'KNU12' ${\times}$ 'AV107-4' 또는 'RPL2'로 판단되었다. 시들음역병의 경우 내병성 공여친인 'L3708'은 야생종으로서 모든 회복친 계통들과 유전적 거리가 매우 멀었으며, 적절한 조합은 유사도 값이 0.41이며 계통 간 45개의 다형성 SSR 마커가 선발된 'L3708' ${\times}$ 'AV107-4'로 판단되었다.

• Journal of Hospice and Palliative Care
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• 제16권4호
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• pp.205-215
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• 2013

말기암환자들은 암의 진행으로 인한 여러 가지 육체적, 정신적 증상들로 고통 받고 있으며, 통증뿐만 아니라 피로감, 쇠약감, 식욕부진, 오심 구토, 호흡곤란 등은 말기암환자의 삶의 질 감소에 큰 영향을 미친다. 피로감은 여러 기전 및 원인에 의하여 발생하는데, 치료 가능한 원인으로는 약물부작용, 빈혈, 심한 통증, 수면장애, 우울증 또는 불안감, 영양부족, 내과적 동반질환 등이다. 피로감의 주 기전으로는 사이토카인의 조절이상 및 시상하부-뇌하수체-부신축의 기능부전, serotonin의 조절이상 생체리듬의 파괴, ATP에서의 변화 등이다. 치료는 치료 가능한 원인을 제거하고 환자의 에너지를 보존할 수 있게 하는 방향으로 활동을 계획하고, 교육해야 하며, 약물 치료로는 corticosteroid와 psychostimulants를 사용할 수 있다. 식욕부진과 악액질도 여러 가지 치료 가능한 원인이 있을 수 있는데, 구내염, 구강 캔디다증, 구강 herpes, 구강건조, 변비, 통증과 호흡곤란같이 조절이 안 되는 증상, 섬망, 오심 구토, 우울증, 위장관 운동기능 장애, 역류성 식도염, 내분비 장애가 포함 된다. 식욕부전의 기전은 음식섭취를 조절하는 뇌의 생리적 기전의 이상과 관련, serotonin 분비 증가, IL-$1{\alpha}$, IL-1, IL-6, IL-8 TNF-${\alpha}$와 관련이 있다. 악액질의 기전은 에너지와 기질(substrate metabolism)에서의 변화, 종양에서 생산된 지질분해요소와 단백질 분해요소, 호르몬 이상, 암세포로부터 세포성장에 필요한 영양분을 빼앗기는 것, 에너지 섭취의 감소 등이다. 치료는 정신과 상담 및 환자와 가족의 교육인데, 교육할 때는 환자와 그 가족에게 식욕부진과 악액질이 암으로 인한 임종과정 중 일어나는 자연적인 현상이라는 것을 알리며, 다른 행동으로 환자를 돌보는 방법 등을 교육한다. 약물치료로는 megestrol acetate와 dronabinol, steroid를 사용할 수 있다. 오심 구토의 원인 중 치료가 가능할 수도 있는 것으로는 약물, 요독증, 감염, 불안증, 변비, 상부위장관 폐쇄, 고칼슘혈증, 저나트륨증이 있고, 치료는 metoclopramide, haloperidol, olanzapine 또는 ondansetron 등을 사용해 볼 수 있다. 말기 암에서 호흡곤란의 증상은 폐의 특별한 병변이 없이도 환자가 호소할 수 있는데, 이 경우 opioids가 효과적이다. 말기 암환자에서 환자의 증상을 경감시켜주기 위한 완화치료는 매우 중요하며, 환자의 증상을 잘 평가하고 적절한 치료 및 관리를 해 줌으로써 환자의 삶의 질을 향상시킬 수 있다. 따라서 이들 환자의 증상 호소에 더욱 관심을 갖고 적극적으로 치료하고 관리하여야 할 것이다.