• Journal of Microbiology and Biotechnology
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• 제17권12호
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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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• 제42권11호
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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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• 제15권3호
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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.

• IMMUNE NETWORK
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• 제21권4호
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• pp.26.1-26.28
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• 2021

Asthma exacerbations are a major cause of intractable morbidity, increases in health care costs, and a greater progressive loss of lung function. Asthma exacerbations are most commonly triggered by respiratory viral infections, particularly with human rhinovirus (hRV). Respiratory viral infections are believed to affect the expression of indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in tryptophan catabolism, which is presumed to alter asthmatic airway inflammation. Here, we explored the detailed role of IDO in the progression of asthma exacerbations using a mouse model for asthma exacerbation caused by hRV infection. Our results reveal that IDO is required to prevent neutrophilic inflammation in the course of asthma exacerbation caused by an hRV infection, as corroborated by markedly enhanced Th17- and Th1-type neutrophilia in the airways of IDO-deficient mice. This neutrophilia was closely associated with disrupted expression of tight junctions and enhanced expression of inflammasome-related molecules and mucin-inducing genes. In addition, IDO ablation enhanced allergen-specific Th17- and Th1-biased CD4⁺ T-cell responses following hRV infection. The role of IDO in attenuating Th17- and Th1-type neutrophilic airway inflammation became more apparent in chronic asthma exacerbations after repeated allergen exposures and hRV infections. Furthermore, IDO enzymatic induction in leukocytes derived from the hematopoietic stem cell (HSC) lineage appeared to play a dominant role in attenuating Th17- and Th1-type neutrophilic inflammation in the airway following hRV infection. Therefore, IDO activity in HSC-derived leukocytes is required to regulate Th17- and Th1-type neutrophilic inflammation in the airway during asthma exacerbations caused by hRV infections.

• Molecules and Cells
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• 제42권3호
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• pp.228-236
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• 2019

CD4 T cells differentiate into $ROR{\gamma}t/IL$-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.

• Journal of Preventive Veterinary Medicine
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• 제43권4호
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• pp.214-220
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• 2019

Although canine brucellosis has been known to be an important re-emerging zoonosis, the pathophysiological mechanisms of Brucella canis infection remains clues to be solved. Different culture models, single and co-culture models, were constructed with canine epithelial cells, D17 and macrophage, DH82 to investigate the induction of immune responses in in vivo B. canis infection. Expression of genes related with induction of immune responses, Th1, Th2 and Th17, was compared in the two different models after the bacterial infection. In this study, expression of cytokine genes, IL-1β, IL-5, IL-6, IL-10, IL-23, and TNF-α was quantified in the DH82 at different time points using RT-qPCR in the two different culture systems after the infection. Cytokine genes related with Th1, IL-1β and TNF-α and Th17, IL-6 and IL-23 were expressed with time-dependent manners in the both systems (p<0.05). However, increase of Th2-related cytokine genes expression was not detectable in the both systems by comparison with control. The expression of Th1 and Th17 related cytokine genes was earlier in single cell culture than those in co-culture model (p<0.05). In general, amounts of the expressed genes were shown higher in single cell model than those in co-culture models. This study indicate that Th1 and Th17-associated immune responses are central to B. canis infection in dogs. In addition, it suggests a specific role of epithelial cells in the B. canis infection in vivo, which should resolved in the further study.

• BMB Reports
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• 제42권12호
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• pp.776-787
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• 2009

T helper (Th) 17 cells have recently been described as a third subset of T helper cells, and have provided new insights into the mechanisms that are important in the development of autoimmune diseases and the immune responses that are essential for effective antimicrobial host defense. Both protective and harmful effects of Th17 responses during infection have been described. In general, Th17 responses are critical for mucosal and epithelial host defense against extracellular bacteria and fungi. However, recent studies have reported that Th17 responses can also contribute to viral persistence and chronic inflammation associated with parasitic infection. It has become evident that the type of microorganisms and the setting in which they trigger the Th17 response determines the outcome of the delicate balancethat exists between Th17 induced protection and immunopathogenesis.

• Journal of Ginseng Research
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• 제40권1호
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• pp.18-27
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• 2016

Background: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. Methods: Using CD4+ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naïve T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. Results: Under TCR stimulation, KRGE treatment did not affect the population of CD4+interferon gamma ($IFN{\gamma}$)+ and CD4+interleukin (IL)-4+ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4+IL-17+ cells and CD4+/phosphorylated STAT3 (p-STAT3)+ cells, but increased the number of CD4+CD25+forkhead box P3 (Foxp3)+ cells and CD4+/p-STAT5+ cells compared with CsA alone. In allogeneic APCs-stimulated CD4+ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4+IL-17+ cells and increased the number of CD4+CD25+Foxp3+ cells under the Th17-polarizing condition. Conclusion: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression.

• Asian-Australasian Journal of Animal Sciences
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• 제13권2호
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• pp.161-166
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• 2000

This study was designed to determine the effects of the insulin-like growth factor (IGF-1) and estradiol $17-{\beta}$ on the in vitro proliferation of stromal vascular cell from Hanwoo omental, subcutaneous, intermuscular and intramuscular adipose tissues. Cells were cultured in M199+20% newborn calf serum and the proliferation of cells was measured by direct microscopic cell counting and change of genomic DNA amount. Cell numbers increased slightly over the first 72 hour of culture and then increased greatly, regardless of adipose tissue depots. In IGF-1 treatment, the number of omental preadipocytes maintained highest level from the beginning to the 20th day of culture. However, in estradiol-$17{\beta}$ treatment, those tended to be lower than the control from the beginning of culture and significantly lower at the 24th day. When IGF-1 was added to subcutaneous preadipocytes, the numbers of cells were higher from 11th day than those from other treatments, although there was no statistical significance. For intermuscular preadipocytes treated with IGF-1, its numbers were significantly (p<0.05) higher at 11th day, and in the other days it showed a similar tendency to those of the subcutaneous tissue. In this experiment, preadipocytes were taken from 24 month old fully matured steers and the highest proliferation rate was shown in intramuscular tissue followed by those of subcutaneous preadipocytes. Addition of $5{\mu}M$ estradiol-$17{\beta}$ to the growth medium failed to promote the replication of Hanwoo preadipocytes, as indicated by direct cell counts and total genomic DNA content. As the culture period proceeded, the amounts of DNA were increased, but the patterns of increment were not consistent with the results of cell numbers.

• Molecules and Cells
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• 제44권5호
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• pp.318-327
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• 2021

CD4+ T helper (Th) cells play a crucial role in the modulation of innate and adaptive immune responses through the differentiation of Th precursor cells into several subsets, including Th1, Th2, Th17, and regulatory T (Treg) cells. Effector Th and Treg cells are distinguished by the production of signature cytokines and are important for eliminating intracellular and extracellular pathogens and maintaining immune homeostasis. Stimulation of naive Th cells by T cell receptor and specific cytokines activates master transcription factors and induces lineage specification during the differentiation of Th cells. The master transcription factors directly activate the transcription of signature cytokine genes and also undergo post-translational modifications to fine-tune cytokine production and maintain immune balance through cross-regulation with each other. This review highlights the post-translational modifications of master transcription factors that control the differentiation of effector Th and Treg cells and provides additional insights on the immune regulation mediated by protein argininemodifying enzymes in effector Th cells.