Hwa-Jung Yi

Gwangju Institute of Science and Technology, Kwangju, Gwangju, South Korea

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Publications (5)15.23 Total impact

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    ABSTRACT: Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are antibody-mediated autoimmune diseases in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen. Previously we have revealed that oral treatment with the less native recombinant fragment of the extracellular domain of the human AChR (Halpha1-205) suppressed ongoing EAMG, whereas the more native recombinant Trx-Halpha1-210 exacerbated EAMG. In this study, we speculated on the role of B-cell epitopes in oral tolerogens for the induction of oral tolerance in EAMG. We developed a B-cell epitope-free AChR fragment (BF-AChR) by removing two major B-cell epitopes (67-76 and 129-145) from Trx-Halpha1-210. BF-AChR exhibited a poor response to EAMG sera and to AChR-specific B- and T-cells while its parent fragment, Trx-Halpha1-210, showed much higher reactivity. Oral administration of BF-AChR ameliorated the symptoms in ongoing myasthenic rats accompanied by a significant decrease in AChR-specific humoral and Th1 cellular responses. The underlying mechanism for BF-AChR-induced oral tolerance was mediated by a shift from Th1 to regulatory T-cell (IL-10(+), CD4(+) TGF-beta(+) or Foxp3(+)) responses. This shift was assessed by changes in the cytokine profile and a deviation in the anti-AChR IgG isotypes from IgG2a/IgG2b to IgG1. Our results suggest that the removal of pathogenic B-cell epitopes from AChR fragments increases tolerogenicity by reducing the activation and proliferation of autoreactive B- and T-cells. Collectively, careful consideration of the immunogenicity of a tolerogen is necessary to induce successful oral tolerance in autoimmune disorders.
    Molecular Immunology 10/2008; 46(1):192-201. · 2.65 Impact Factor
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    ABSTRACT: Probiotics have been shown to exert beneficial effects on modulation of diverse diseases. However, no information is available for the effect of probiotics in the induction of oral tolerance in autoimmune diseases. The main purpose of this study was to elucidate whether Lactobacillus casei (L. casei) affect the induction of oral tolerance in experimental rheumatoid arthritis (RA). Type II collagen (CII) alone or together with L. casei was orally administered into collagen-induced arthritis (CIA) rats, and its effects on the clinical and histopathological aspects of RA were investigated. Co-administration of L. casei with CII more effectively suppressed clinical symptoms, paw swelling, lymphocyte infiltration and destruction of cartilage tissues of experimental arthritis than the rats treated with CII alone. The enhanced therapeutic efficacy was associated with an increase in anti-inflammatory cytokines (IL-10 and TGF-beta) while decreasing pro-inflammatory cytokines (IL-1beta, IL-2, IL-6, IL-12, IL-17, IFN-gamma and TNF-alpha). Co-administration of L. casei with CII more effectively suppressed CII-reactive T cell proliferation and the levels of Th1-type IgG isotypes (IgG2a and IgG2b), while up-regulating Foxp3 expression levels and the population of Foxp3(+) CD4(+) T cells. Our study provides evidence that L. casei could potentiate antigen-specific oral tolerance and suppress Th1-type immune responses of arthritic inflammation.
    Molecular Immunology 10/2008; 46(1):172-80. · 2.65 Impact Factor
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    ABSTRACT: Alternative splicing of mRNA enables functionally diverse protein isoforms to be expressed from a single gene, allowing transcriptome diversification. Interleukin (IL)-24/MDA-7 is a member of the IL-10 gene family, and FISP (IL-4-induced secreted protein), its murine homologue, is selectively expressed and secreted by T helper 2 lymphocytes. A novel splice variant of mouse IL-24/FISP, designated FISP-sp, lacks 29 nucleotides from the 5'-end of exon 4 of FISP. The level of FISP-sp expression is 10% of the level of total primary FISP transcription. Unlike FISP, FISP-sp does not induce growth inhibition and apoptosis. FISP-sp is exclusively localized in endoplasmic reticulum, and its expression is up-regulated by endoplasmic reticulum stress. Our results suggest that the novel splicing variant FISP-sp dimerizes with FISP and blocks its secretion and inhibits FISP-induced apoptosis in vivo.
    Journal of Biological Chemistry 09/2008; 283(43):28860-72. · 4.65 Impact Factor
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    ABSTRACT: Mesenteric lymph node (MLN) in gut-associated lymphoid tissue plays obligatory roles in the induction of oral tolerance and ignorance to commensals. However, little is known about its immunological characteristics. In this study, we investigated the hypo-responsiveness of MLN CD4(+) T cells, comparing them with spleen CD4(+) T cells. MLN CD4(+) T cells were hypo-proliferative and expressed low levels of Th1-type cytokines in response to antigen or CD3/T cell receptor (TCR) stimulation. The hypo-responsiveness of MLN CD4(+) T cells is linked neither with changes in the regulatory T cell population (CD4(+)CD25(+), CD4(+)Foxp3(+)) nor the apoptotic population. Rather, MLN CD4(+) T cells showed deformity of T cell:APC conjugation and reduced expression of TCR signaling molecules such as CD3zeta, PLC-gamma1, PKC-theta, Zap70, with reduced phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs). Among the alterations in TCR signaling molecules, defective CD3zeta expression is the most evident, and reversal of the anergic state by CD3/CD28 costimulation restored CD3zeta expression levels. Collectively, we suggest that reduced CD3zeta expression and defects in TCR signaling mediate the anergy state of MLN CD4(+) T cells, which play a critical role in maintenance of mucosal tolerance in gut-associated lymphoid tissue.
    Molecular Immunology 08/2008; 45(14):3748-55. · 2.65 Impact Factor
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    ABSTRACT: Although the beneficial effects of probiotics on wide variety of diseases have been shown, little is known about how probiotics modulate the immune system. In this study we elucidated the underlying mechanisms how Lactobacillus casei (L. casei) protects against rheumatoid arthritis (RA) progression by investigating the effector functions of CD4(+) T cells. Oral administration of L. casei suppressed collagen-induced arthritis (CIA) and reduced paw swelling, lymphocyte infiltration and destruction of cartilage tissue. L. casei administration reduced type II collagen (CII)-reactive proinflammatory molecules (IL-1beta, IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha and Cox-2) by CD4(+) T cells. L. casei administration also reduced translocation of NF-kappaB into nucleus and CII-reactive Th1-type IgG isotypes IgG2a and IgG2b, while up-regulating immunoregulatory IL-10 levels. Our results suggest that oral administration of L. casei suppresses the type II collagen-reactive effector function of Th1-type cellular and humoral immune responses in arthritic inflammation.
    Molecular Immunology 06/2008; 45(9):2690-9. · 2.65 Impact Factor