• IMMUNE NETWORK
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• v.11 no.6
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• pp.416-419
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• 2011

Dextran sodium sulfate (DSS) is a widely used chemical model for inflammatory bowel disease (IBD). It is thought that imbalances in the T helper (Th) cell subsets contribute to IBD. Recent studies suggest that the acute DSS-colitis model is polarized toward a Th1/Th17 profile based on RT-PCR analysis of colonic tissues. In the current study we determined whether colonic Th cells from DSS-colitis mice were skewed toward the Th17 profile. Mice were treated with 5% DSS for 7 days and colonic T cells isolated and examined for production of IFN-${\gamma}$ (Th1 cell), IL-4 (Th2 cell) and IL-17 (Th17 cell) by intracellular flow cytometry. We found that the percentage of colonic Th17 cells were similar to non-treated controls but the percentage of Th1 cells were elevated in DSS-colitis mice. These results suggest that in the acute DSS-colitis model the colonic Th cells exhibit a Th1 profile and not a Th17 profile.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.71-76
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• 2015

Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed $PPAR{\gamma}$-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a $PPAR{\gamma}$ ligand, reduced both IL-$1{\beta}$-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-$1{\beta}$. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical $PPAR{\gamma}$ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.

• IMMUNE NETWORK
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• v.14 no.1
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• pp.14-20
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• 2014

CD28/T cell receptor ligation activates the NF-${\kappa}B$ signaling cascade during CD4 T cell activation. NF-${\kappa}B$ activation is required for cytokine gene expression and activated T cell survival and proliferation. Recently, many reports showed that NF-${\kappa}B$ activation is also involved in T helper (Th) cell differentiation including Th17 cell differentiation. In this review, we discuss the current literature on NF-${\kappa}B$ activation pathway and its effect on Th17 cell differentiation.

• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.466-473
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• 2019

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

• Korean Journal of Plant Resources
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• v.27 no.5
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• pp.567-575
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• 2014

Resveratrol is a naturally occurring stilbene which is safe and well-described compound with a potent anti-inflammatory activity. Recent studies suggested that resveratrol suppressed various inflammation mediated diseases such as asthma, chronic colitis, rheumatoid arthritis, and type 1 diabetes. These studies indicated that resveratrol might directly modulate $CD4^+$ helper T cells (Th cells)-mediated immune responses. However, it is not fully elucidated whether resveratrol directly regulates $CD4^+$ Th cell activation and differentiation. In the present study, $CD4^+$ Th cells were purified from C57BL/6 and treated with various concentrations of resveratrol. We found that resveratrol directly suppressed $CD4^+$ Th cells activation, leading to a defect in T cell proliferation. When $CD4^+$ Th cells were treated with resveratrol, cytokine production was also significantly reduced in a dose dependent manner. In accordance with these results, resveratrol even inhibited $CD4^+$ Th cells differentiation into Th1, Th2 or Th17, which produces IFN-${\gamma}$, IL-4 or IL-17 respectively. We also found that resveratrol could induce apoptosis of $CD4^+$ T cells at a high concentration. Our data demonstrated that resveratrol inhibited directly $CD4^+$ Th cells activation and differentiation. It suggests that resveratrol could be an efficient therapeutic strategy for autoimmune diseases in which $CD4^+$ Th cells play a critical role.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.638-649
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• 2016

In the previous study, the rhizome mixture of Anemarrhena asphodeloides and Coptis chinensis (DW2007), improved TNBS-, oxazolone-, or DSS-induced colitis in mice by regulating macrophage activation. Therefore, to understand the effect of DW2007 on the T cell differentiation involved in the adaptive immunity, we measured its effect on both Th17 and Treg cell differentiation in splenocytes, in the lamina propria of mice with DSS-induced colitis (DIC), and in the spleens of mice with collagen-induced arthritis (CIA). Results showed that DW2007 potently inhibited the differentiation of splenocytes into Th17 cells, but increased Treg cell differentiation in vitro. In the colon of wild type and $TLR4^{-/-}$ mice with DIC, DW2007 potently suppressed DSS-induced colon shortening and myeloperoxidase activity. DW2007 also suppressed collagen-induced paw thickening, clinical index, and myeloperoxidase activity in CIA mice. Overall, DW2007 potently suppressed Th17 cell differentiation in mice with CIA and DIC, but increased Treg cell differentiation. Moreover, DW2007 strongly inhibited the expression of TNF-${\alpha}$ and IL-$1{\beta}$, as well as the activation of NF-${\kappa}B$. Based on these findings, DW2007 may ameliorate inflammatory diseases by regulating the innate immunity via the inhibition of macrophage activation and the adaptive immunity via the correction of disturbed Th17/Treg cells.

• Animal Bioscience
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• v.36 no.1
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• pp.156-166
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• 2023

Objective: In this study, we investigated the effects of Rubus coreanus-derived lactic acid bacteria (LAB) fermented feed (RC-LAB fermented feed) and three types of LAB (Lactobacillus plantarum, Lactobacillus acidophilus, Bifidobacterium animalis) on the expression of transcription factors and cytokines in Th1, Th2, Th17, and Treg cells in the intestinal lymph nodes and spleens of rats. In addition, the effect on intestinal microbiota composition and body weight was investigated. Methods: Five-week-old male rats were assigned to five treatments and eight replicates. The expression of transcription factors and cytokines of Th1, Th2, Th17, and Treg cells in the intestinal lymph nodes and spleens was analyzed using real-time reverse transcriptase polymerase chain reaction assays. Intestinal tract microbiota compositions were analyzed by next-generation sequencing and quantitative polymerase chain reaction assays. Results: RC-LAB fermented feed and three types of LAB increased the expression of transcription factors and cytokines in Th1, Treg cells and Galectin-9, but decreased in Th2 and Th17 cells. In addition, the intestinal microbiota composition changed, the body weight and Firmicutes to Bacteroidetes (F/B) ratio decreased, and the relative abundance of LAB increased. Conclusion: LAB fermented feed and three types of LAB showed an immune modulation effect by inducing T cell polarization and increased LAB in the intestinal microbiota.

• Journal of Microbiology and Biotechnology
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• v.17 no.12
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• pp.2056-2060
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• 2007

Transcription factor GATA-3 is the critical transcription factor for Th2 cell differentiation. In spite of its importance in Th2 cell differentiation, the molecular mechanism for its action in Th2 differentiation is poorly understood. Previous studies have suggested that GATA-3 may be involved in the chromatin remodeling in the Th2 cytokine locus. To determine whether GATA-3 exerts its effect on its target sites in the extrachromosomal status, cell transfection assay was performed. In this assay, 800 bp IL4 promoter-luciferase constructs linked with GATA-3 target sites were transfected into the M12 B cell line, D10 mouse Th2 cell lines, and human T lymphoma Jurkat cell lines with or without the GATA-3 expression vector. The GATA-3 effects on its target sites were minimal in the extrachromosomal status, supporting the previous propositions that GATA-3 functions at the chromatin level by remodeling chromatin structure.

• Molecules and Cells
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• v.42 no.11
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• pp.747-754
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• 2019

The incidence of atherosclerosis is higher among patients with several autoimmune diseases such as psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is well documented that innate immune cells including macrophages and dendritic cells sense lipid species such as saturated fatty acids and oxidized low-density lipoprotein and produce pro-inflammatory cytokines and chemokines. However, whether a hyperlipidemic environment also impacts autoimmune T cell responses has been unclear. Among $CD4^+$ T cells, Th17 and follicular helper T (Tfh) cells are known to play pathogenic roles in the development of hyperlipidemia-associated autoimmune diseases. This review gives an overview of the cellular and molecular mechanisms by which dysregulated lipid metabolism impacts the pathogenesis of autoimmune diseases, with specific emphasis on Th17 and Tfh cells.

• IMMUNE NETWORK
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• v.15 no.3
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• pp.142-149
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• 2015

Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPNdeficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and IL-17-producing ${\gamma}{\delta}$ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and the percentage of IFN-$\gamma$-producing ${\gamma}{\delta}$ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in $CD4^+$ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-$\gamma$ T cells.