• 한양메디칼리뷰
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• 제33권1호
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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.

• 대한이식학회지
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• 제31권4호
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• pp.157-169
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• 2017

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.

• Journal of Veterinary Science
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• 제25권3호
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• pp.35.1-35.13
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• 2024

Importance: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. Objective: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. Methods: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein_35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. Results: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. Conclusions and Relevance: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

• IMMUNE NETWORK
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• 제24권1호
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• pp.10.1-10.17
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• 2024

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

• Clinical Endoscopy
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• 제56권4호
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• pp.510-520
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• 2023

Background/Aims: We aimed to investigate (1) promising clinical findings for the recognition of focal type autoimmune pancreatitis (FAIP) and (2) the impact of endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA) on the diagnosis of FAIP. Methods: Twenty-three patients with FAIP were involved in this study, and 44 patients with resected pancreatic ductal adenocarcinoma (PDAC) were included in the control group. Results: (1) Multivariate analysis revealed that homogeneous delayed enhancement on contrast-enhanced computed tomography was a significant factor indicative of FAIP compared to PDAC (90% vs. 7%, p=0.015). (2) For 13 of 17 FAIP patients (76.5%) who underwent EUS-TA, EUS-TA aided the diagnostic confirmation of AIPs, and only one patient (5.9%) was found to have AIP after surgery. On the other hand, of the six patients who did not undergo EUS-TA, three (50.0%) underwent surgery for pancreatic lesions. Conclusions: Homogeneous delayed enhancement on contrast-enhanced computed tomography was the most useful clinical factor for discriminating FAIPs from PDACs. EUS-TA is mandatory for diagnostic confirmation of FAIP lesions and can contribute to a reduction in the rate of unnecessary surgery for patients with FAIP.

• Molecules and Cells
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• 제42권12호
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• pp.906-918
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• 2019

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

• Clinical and Experimental Pediatrics
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• 제48권3호
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• pp.292-297
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• 2005

대 상 : 1981년 1월부터 2004년 7월까지 서울대학교병원 소아과에서 추적 중인 1형 당뇨병 환자 일부에서 후향적으로 의무기록 분석을 시행하였다. 방 법 : Anti-TG Ab, anti-TPO Ab를 방사면역방법으로 측정하였으며, 둘 중 하나라도 양성인 경우에는 자가면역성 갑상선염이 있는 군(갑상선 질환군)으로 정의하였다. 두 항체 모두 음성이며, 갑상선 수용체 항체(TSHRAb)가 음성인 경우는 자가면역성 갑상선 질환이 없는 군(갑상선 비질환군)으로 정의하였다. TSHRAb가 양성인 Graves병 환자는 갑상선 질환군에 포함시켰다. 결 과 : 총 139명에서 검사를 시행하였으며, 남아 44명(연령 $14.4{\pm}4.8$, 5.9-26.6세), 여자 95명(연령 $13.6{\pm}5.4$세, 3.6-30세)이었다. 갑상선 질환군과 비 갑상선 질환군에서 성비, 당화혈색소, 체질량지수, 당뇨병의 발병연령, 갑상선 질환의 가족력에서 두 군 간에 통계적으로 유의한 차이는 없었다. 갑상선 질환은 남자에서는 역연령 5.0-9.9세 사이에서 검사한 환자의 42.8%에서 발견되었고 여자에서는 역연령 10-14.9세, 15-19.9세에서 각각 56.5%와 50.0%에서 발견되어 남자가 여자에 비해 상대적으로 낮은 연령에서 흔하게 발생하였다. 자가면역성 갑상선 질환은 갑상선종이 있는 경우에서 없는 경우보다 흔하게 발견되었고 갑상선종이 동반된 경우에 남녀간의 발생빈도의 차이는 없었다. 갑상선 기능은 정상 기능을 유지하는 경우가 74%였고, 기능저하와 기능항진은 각각 13%로 동일한 비율을 보였다. 결 론 : 1형 당뇨병 환자에서는 10세 이상의 연령에서 갑상선 기능검사와 자가항체검사가 필요한데 특히, 갑상선종이 발견되거나 남아에서는 최소 8세가 되면 갑상선 기능검사와 항체검사를 시행하고 지속적으로 추적하는 것이 바람직할 것으로 생각된다.

• 식품과학과 산업
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• 제55권3호
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• pp.276-283
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• 2022

비타민D3는 칼슘 대사를 조절하며 뼈의 건강을 담당하는 중요한 호르몬이지만 다양한 면역세포에 작용하여 면역반응을 조절할 수 있다는 것이 알려지면서 자가면역질환, 알레르기질환, 감염 등 여러 질병과의 상관관계에 대한 관심이 증가되었다. 비타민D3의 활성 형태인 1,25(OH)2D3는 면역세포에 의해 전환될 수 있으며 핵-호르몬 수용체인 VDR과 결합하여 세포 내 다양한 유전자 발현을 조절함으로써, 세포의 형질과 기능을 바꿀 수 있다. 특히, 최근 다양한 연구를 통해 과도한 면역 반응을 조절하는 Treg 세포의 분화를 증가시키고 그 기능을 향상시키는 기전을 통해 염증성 사이토카인을 감소시키며, 외부 병원균을 제거할 수 있는 AMP의 생산을 유도함으로써 자가면역질환, 알레르기, 감염성 질환 등 다양한 질환에 긍정적 역할을 할 수 있음이 확인되었다. 특히, 최근 COVID-19 에 의한 글로벌 팬데믹을 경험하면서, 중증 질환 및 사망에 이르는 환자들과 비타민D의 상관관계 연구, 다양한 나라들에서 시행된 비타민D 치료의 임상결과들을 통해, 비타민D 보충 기반의 면역조절의 전략이 유리할 수 있음을 알 수 있었다. 전세계 현대인들의 비타민D 결핍은 최근 50년 간 지속적으로 증가하고 있으며, 자외선 노출로 합성할 수 있는 비타민D의 양이 충분하지 않은 부분을 식품 또는 보충제의 형태로 섭취하는 것이 여러 자가면역질환과 알레르기, 감염성 질병을 예방하는데 도움이 될 것이다.

• IMMUNE NETWORK
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• 제10권3호
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• pp.81-84
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• 2010

B cells, by virtue of their diverse roles in immune responses to foreign and self antigens, have become of increasing interest to the clinician as well as the basic immunologist. In particular, it is now apparent that the development of B cell unresponsiveness in antibody and T cell mediated autoimmune disorders and the transplant setting is both worthwhile and achievable.

• Annals of Clinical Neurophysiology
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• 제23권1호
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• pp.1-6
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• 2021

Postural tachycardia syndrome (POTS) is the most common form of orthostatic intolerance in young people. However, it is still considered an underrecognized disorder and so deserves more attention from clinicians. This review covers the diagnostic challenges, correlations between the symptoms, evidence of autoimmune involvement in the pathogenesis, and treatment strategies in POTS.