• Hanyang Medical Reviews
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• v.33 no.1
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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.

• Korean Journal of Transplantation
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• v.31 no.4
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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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• v.25 no.3
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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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• v.24 no.1
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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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• v.56 no.4
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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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• v.42 no.12
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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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• v.48 no.3
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• pp.292-297
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• 2005

Purpose : It is known that 3-50 percent of type 1 diabetes mellitus(T1DM) patients develop autoimmune thyroid disease. We analyzed the clinical characteristics of autoimmune thyroid disease(AITD) developed in patients with T1DM in Korean. Methods : The medical records of 139 patients, who were followed up in Department of Pediatrics, Seoul National University Children's Hospital from Jan. 1981 to Jul. 2004, were analyzed retrospectively. Results : Forty-four males and 95 females were enrolled. At least one of the autoantibodies for thyroid was positive in 54 cases. The detection rate for AITD was not correlated with sex ratio, control of T1DM, body mass index, age at diagnosis of T1DM, and familial history of thyroid disease, between two groups. In the male group, AITD was more frequently found at a younger age than in the female group. The frequency of AITD was significantly higher in the goiter group without sex differences. In the thyroid disease group, 40 patients(74.0 percent) were euthyroid, seven patients(12.9 percent) were hypothyroid, and seven patients(12.9 percent) were hyperthyroid. Conclusion : We should monitor thyroid function and autoantibodies routinely in T1DM patients who develop goiters, or young boys with T1DM.

• Food Science and Industry
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• v.55 no.3
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• pp.276-283
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• 2022

Vitamin D is a fat-soluble vitamin helps to retain calcium and phosphorus but also has shown to affect immune regulation and homeostasis. In humans, vitamin D3 and vitamin D2 and their metabolite has intensively studied in both innate and adaptive immune system that they are important to regulate overwhelmed inflammation. The vitamin D receptor is a nuclear hormone receptor which regulate various downstream target gene expressions as a transcription factor related to metabolism, immune regulation, etc. Vitamin D deficiency is a high-risk factor for inflammatory diseases like autoimmune disease and allergy. In addition, reduced vitamin D seem to correlate with susceptibility to the virus infection such as HIV and COVID-19. In this review, we will summarize up-to-date vitamin D's role in various immune cells, immune regulatory functions during autoimmune, allergic, and infectious diseases. We will also discuss about vitamin D supplement effects in human trial studies for COVID-19.

• IMMUNE NETWORK
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• v.10 no.3
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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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• v.23 no.1
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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.