• Archives of Pharmacal Research
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• v.26 no.4
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• pp.312-316
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• 2003

The oriental herbal combination allergina has been shown to inhibit allergic inflammation. In the present study, we demonstrate that the oral administration of allergina markedly inhibits the progression of inflammatory diseases, such as graft-versus-host diseases (in the allogeneic bone marrow transplantation and the parent-into-F1 transplantation models), collagen-induced arthritis and sheep red blood cell-induced delayed type hypersensitivity. The immunosuppressive activity of allergina in vivo appears to be associated, at least in part, with the inhibition of tumor necrosis factor-a production. In conclusion, our results suggest that allergina could be useful as a immunosuppressive agent for the treatment of macrophage-related inflammatory disease.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.428-430
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• 2011

We previously demonstrated that in vivo engagement of CD137, a member of TNF receptor superfamily, can delete allorective $CD4^+$ T cells through the induction of activation-induced cell death (AICD) in chronic graft-versus-host disease (cGVHD) and subsequently reverse established cGVHD. In this study, we further showed that agonistic anti-CD137 mAb was highly effective in triggering AICD of donor $CD8^+$ T cells as well as donor $CD4^+$ T cells in the $C57BL/6{\rightarrow}unirradiated$ $(C57BL/6\;{\times}\;DBA/2)F1$ acute GVHD model. Our results suggest that strong allostimulation should facilitate AICD of both alloreactive $CD4^+$ and $CD8^+$ T cells induced by CD137 stimulation. Therefore, depletion of pathogenic T cells using agonistic anti-CD137 mAb combined with potent TCR stimulation may be used to block autoimmune or inflammatory diseases mediated by T cells.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.133-140
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• 2013

Since the discovery of the immunomodulation property of mesenchymal stem cells (MSCs) about a decade ago, it has been extensively investigated whether MSCs can be used for the treatment of immune-related diseases, such as graft versus-host disease (GvHD). However, how to evaluate the efficacy of human MSCs for the clinical trial is still unclear. We used an MHC-mismatched model of GvHD (B6 into BALB/c). Surprisingly, the administration of the human MSCs (hMSCs) could reduce the GvHD-related mortality of the mouse recipients and xenogeneically inhibit mouse T-cell proliferation and $IFN-{\gamma}$ production in vitro. We recently established a new protocol for the isolation of a homogeneous population of MSCs called subfractionation culturing methods (SCM), and established a library of clonal MSC lines. Therefore, we also investigated whether MSCs isolated by the conventional gradient centrifugation method (GCM) and SCM show different efficacy in vivo. Intriguingly, clonal hMSCs (hcMSCs) isolated by SCM showed better efficacy than hMSCs isolated by GCM. Based on these results, the MHC-mismatched model of GvHD may be useful for evaluating the efficacy of human MSCs before the clinical trial. The results of this study suggest that different MSC lines may show different efficacy in vivo and in vitro.

• IMMUNE NETWORK
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• v.8 no.4
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• pp.107-123
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• 2008

It has now been well documented in a variety of models that T regulatory T cells (Treg cells) play a pivotal role in the maintenance of self-tolerance, T cell homeostasis, tumor, allergy, autoimmunity, allograft transplantation and control of microbial infection. Recently, Treg cell are isolated and can be expanded in vitro and in vivo, and their role is the subject of intensive investigation, particularly on the possible Treg cell therapy for various immune-mediated diseases. A growing body of evidence has demonstrated that Treg cells can prevent or even cure a wide range of diseases, including tumor, allergic and autoimmune diseases, transplant rejection, graft-versus-host disease. Currently, a large body of data in the literature has been emerging and provided evidence that clear understanding of Treg cell work will present definite opportunities for successful Treg cell immunotherapy for the treatment of a broad spectrum of diseases. In this Review, I briefly discuss the biology of Treg cells, and summarize efforts to exploit Treg cell therapy for autoimmune diseases. This article also explores recent observations on pharmaceutical agents that abrogate or enhance the function of Treg cells for manipulation of Treg cells for therapeutic purpose.

• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.183-187
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• 2004

Bronchiolitis obliterans (BO) is a nonspecific inflammatory injury affecting primarily the small airways. Its inflammatory process is characterized by fibrotic obliteration of the lumen of bronchioles. BO can be idiopathic or associated with connective tissue disease, inhaled toxins, infections, drugs, and chronic graft-versus-host-disease (GVHD). Pulmonary complications occur in 40~60% of patients who undergo allogeneic bone marrow transplantation (BMT), causing 10~40% of transplant-related deaths. BO is a characteristic pulmonary complication which occurs usually within a few years after BMT. Documented complications of BO include air-leak syndromes such as pneumomediastinum, subcutaneous emphysema and pneumothorax. We report a case of a 30-year-old male patient with BO due to chronic GVHD after allogenic BMT who presented with recurrent bilateral pneumothoraces.

• Annals of Laboratory Medicine
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• v.38 no.6
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• pp.591-598
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• 2018

Background: Forkhead box P3 (FOXP3) is an important marker of regulatory T cells. FOXP3 polymorphisms are associated with autoimmune diseases, cancers, and allograft outcomes. We examined whether single nucleotide polymorphisms (SNPs) at the FOXP3 locus are associated with clinical outcomes after allogenic hematopoietic stem cell transplantation (HSCT). Methods: Five FOXP3 SNPs (rs5902434, rs3761549, rs3761548, rs2232365, and rs2280883) were analyzed by PCR-sequencing of 172 DNA samples from allogenic HSCT patients. We examined the relationship between each SNP and the occurrence of graft-versus-host disease (GVHD), post-HSCT infection, relapse, and patient survival. Results: Patients with acute GVHD (grades II-IV) showed higher frequencies of the rs3761549 T/T genotype, rs5902434 ATT/ATT genotype, and rs2232365 G/G genotype than did patients without acute GVHD (P =0.017, odds ratio [OR]=5.3; P =0.031, OR=2.4; and P =0.023, OR=2.6, respectively). Multivariate analysis showed that the TT genotype of rs3761549 was an independent risk factor for occurrence of acute GVHD (P =0.032, hazard ratio=5.6). In contrast, the genotype frequencies of rs3761549 T/T, rs5902434 ATT/ATT, and rs2232365 G/G were lower in patients with post-HSCT infection than in patients without infection (P =0.026, P =0.046, and P =0.031, respectively). Conclusions: rs3761549, rs5902434, and rs2232365 are associated with an increased risk of acute GVHD and decreased risk of post-HSCT infection.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.181-181
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• 2002

The herbal combination allergina has been used for the treatment of inflammatory diseases in South Korea. In this study, we investigated the immunosuppressive activities of allergina in more detail. Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation.(omitted)

• Journal of Oral Medicine and Pain
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• v.37 no.3
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• pp.147-154
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• 2012

Hematopoietic stem-cell transplantation (HSCT) is a treatment for immune deficiency, autoimmune diseases, and hematopoietic malignancies. The main complication of allogenic HSCT is graft-versus-host disease (GVHD). Oral mucosal biopsy is needed for a definitive diagnosis and treatment planning of GVHD, but this procedure causes bleeding and bacteremia in a poor general condition. We evaluated the efficacy of laser-assisted biopsy as a minimally invasive treatment. Three cases were described in this article. All patients' medical records, clinical photographs, and histopathologic findings were reviewed. All patients felt comfortable and no severe complications occurred. The quality of the obtained biopsy material was adequate for a definitive diagnosis of GVHD. Laser-assisted, minimally invasive biopsy of the oral mucosa does not cause bleeding, and it reduces the chances of infection, bacteremia, and postoperative scarring compared to the usual histopathologic biopsy procedure. It would thus be advantageous to use this procedure to biopsy GVHD patients.

• Development and Reproduction
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• v.23 no.2
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• pp.79-92
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• 2019

Humanized mice, containing engrafted human cells and tissues, are emerging as an important in vivo platform for studying human diseases. Since the development of Nod scid gamma (NSG) mice bearing mutations in the IL-2 receptor gamma chain, many investigators have used NSG mice engrafted with human hematopoietic stem cells (HSCs) to generate functional human immune systems in vivo, results in high efficacy of human cell engraftment. The development of NSG mice has allowed significant advances to be made in studies on several human diseases, including cancer and graft-versus-host-disease (GVHD), and in regenerative medicine. Based on the human HSC transplantation, organ transplantation including thymus and liver in the renal capsule has been performed. Also, immune reconstruction of cells, of the lymphoid as well as myeloid lineages, has been partly accomplished. However, crosstalk between pluripotent stem cell derived therapeutic cells with human leukocyte antigen (HLA) mis/matched types and immune CD3 T cells have not been fully addressed. To overcome this hurdle, human major histocompatibility complex (MHC) molecules, not mouse MHC molecules, are required to generate functional T cells in a humanized mouse model. Here, we briefly summarize characteristics of the humanized mouse model, focusing on development of CD3 T cells with MHC molecules. We also highlight the necessity of the humanized mouse model for the treatment of various human diseases.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.261.3-262
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• 2002

The herbal combination allergina has been used for the treatment of inflammatory diseases in South Korea. In this study. we investigated the immunosuppressive activities of allergina in more detail. Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation. (omitted)