• Childhood Kidney Diseases
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• v.22 no.1
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• pp.17-21
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• 2018

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.

• Molecules and Cells
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• v.44 no.5
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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.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.171-176
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• 2012

HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as $IFN{\gamma}$, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human ${\beta}2$-defensin (HBD2) in response to $IFN{\gamma}$, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. $IFN{\gamma}$ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to $IFN{\gamma}$, IL-4 or IL-17A.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.344-347
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• 2005

Helper T(Th) cells regulate immune response by producing various kinds of cytokines in response to antigen stimulation. The regulatory functions of Th cells are promoted by their differentiation into two distinct subsets, Th1 and Th2 cells. Th1 cells are involved in inducing cellular immune response by activating cytotoxic T cells. Th2 cells trigger B cells to produce antibodies, protective proteins used by the immune system to identify and neutralize foreign substances. Because cellular and humoral immune responses have quite different roles in protecting the host from foreign substances, Th cell differentiation is a crucial event in the immune response. The destiny of a naive Th cell is mainly controlled by cytokines such as IL-4, IL-12, and IFN-${\gamma}$. To understand the mechanism of Th cell differentiation, many mathematical models have been proposed. One of the most difficult problems in mathematical modeling is to find appropriate kinetic parameters needed to complete a model. However, it is relatively easy to get qualitative or linguistic knowledge of a model dynamics. To incorporate such knowledge into a model, we propose a novel approach, fuzzy continuous Petri nets extending traditional continuous Petri net by adding new types of places and transitions called fuzzy places and fuzzy transitions. This extension makes it possible to perform fuzzy inference with fuzzy places and fuzzy transitions acting as kinetic parameters and fuzzy inference systems between input and output places, respectively.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1397-1403
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• 2004

By recently study, GM (Gamipaemo-tang) treatment have worked well on the allergic asthma. The purpose of this study was effect of GM extract on helper T cell, major regulator of immune system. Splenic cells from 8-week BALB/c mice were cultured in GM containing media without activation for 48 hours. The MTS assay and flow cytometry study revealed that lymphocyte treated with GM were not effective on CD4+ T cells. Subsequently CD4+ T cells were isolated and cultured in GM containing media. Either GM were not effective on CD4+ T cell without APCs. By FACS scan analysis, the expression of INF-γ, IL-4 were down-regulated in the condition skewed Th1 and Th2 cells respectively, Using ELISA analysis, the expression of INF-γ is up-regulated and IL-4 is down-regulated in the condition skewed Th1, Th2 cells respectively. With RT-PCR analysis, the expression of mRNA for INF-γ is down-regulated and IL-4 is down-regulated in the condition skewed Th1 and Th2 cells respectively. The result suggests that GM inhibited the differetiation of Th2 cells significantly and indicates GM could enhance anti-allergic immune system.

• Journal of Physiology & Pathology in Korean Medicine
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• v.38 no.1
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• pp.16-21
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• 2024

Haepyoijin-tang and its main components have been used for phlegm, cough and dyspnea. Using a respiratory inflammation model, we intend to reveal the anti-inflammatory effect and pharmacological mechanism of Haepyoijin-tang. We induced the respiratory inflammation model by Aspergillus oryzae protease and ovalbumin administration. Female Balb/c mice (8 weeks old) were classified into four groups as follows: saline control group, aspergillus oryzae protease and ovalbumin induced respiratory inflammation group (vehicle), inflammation with Haepyoijin-tang (200 mg/kg) administration group, inflammation with dexamethasone (5 mg/kg) administration group (n=7). To identify the anti-inflammatory effects of Haepyoijin-tang water extracts, we measured the inflammatory cell number in bronchoalveolar lavage fluid (BALF) and total live lung cell number. In addition, we checked eosinophil ratio and number in BALF. And Interleukin (IL)-5 level was also measured in lung cell culture supernatant. To confirm the mechanism of anti-inflammatory effects, we analyzed the activated helper T cell (CD4⁺CD25⁺ cell) and Th2 cell (CD4⁺GATA3⁺ cell) ratio and number in lung by using flow cytometry. Finally, we attempted to confirm the immune mechanism by measuring the ratio and number of regulatory T cells (CD4⁺Foxp3⁺ cell). Haepyoijin-tang extracts treatment diminished inflammatory cell, especially, eosinophil number in BALF and total live lung cell number. Moreover, IL-5 level was reduced in Haepyoijin-tang treated group. Surprisingly, Haepyoijin-tang extracts administration not only decreased the activated helper T cell but also Th2 cell population in lung. Additionally, regulatory T cell population was increased in Haepyoijin-tang administration group. Our findings proved that Haepyoijin-tang extract have anti-inflammatory efficacy by suppressing Th2 cell activation and promoting regulatory T cell population.

• The Korea Journal of Herbology
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• v.29 no.6
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• pp.27-33
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• 2014

Objectives : The aims of this study were to exploring the therapeutic effect of Imperatae Rhizoma Extract(IRE) on Asthma. Methods : To investigate biological modulation activities of IRE, we conducted the cell-based assay whether IRE could regulate T helper 2 cells activity with EL4 T cells and mouse splenocytes, and followed animal study to conform the efficacy of their therapeutic potential on OVA-induced asthmatic mouse. Results : In cell study, IRE suppress the nuclear translocation of GATA binding protein-3 protein in phorbol 12-myristate 13-acetate/Ionomycin-stimulated EL4 T cells and Interleukine(IL)-4, IL-5 and IL-13 production in splenocytes at concentration dependent manner. In animal study, IRE-treated groups both 100mg/ml and 200mg/ml improve airway hypersensitibility reaction(AHR) response to methacholine about 30% and 40% with positive control group. Peritoneal blood analysis reveal that eosinophil number and ovalbumin-specific IgE is reduced by IRE treatment. Cell number of eosinophil is also reduced in bronchoalveolar lavage of IRE group like to peritoneal cell and real time-polymerase chain reaction data show that expression levels of IL-4, IL-5 and IL-13 were down regulated in lung tissue. Finally, histological analysis indicate that IRE protect the bronchial tissue damages through the accumulation of inflammatory cells and collagen, and these effect may be cause by interfering Th2 cells activity. Conclusions : Our data represent that IRE potentiates therapeutic activities to the allergic diseases such as asthma by regulating Th2 cells differentiation.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.4.1-4.15
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• 2023

Th cells, which orchestrate immune responses to various pathogens, differentiate from naive CD4 T cells into several subsets that stimulate and regulate immune responses against various types of pathogens, as well as a variety of immune-related diseases. Decades of research have revealed that the fate decision processes are controlled by cytokines, cytokine receptor signaling, and master transcription factors that drive the differentiation programs. Since the Th1 and Th2 paradigm was proposed, many subsets have been added to the list. In this review, I will summarize these events, including the fate decision processes, subset functions, transcriptional regulation, metabolic regulation, and plasticity and heterogeneity. I will also introduce current topics of interest.

• Biomedical Science Letters
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• v.21 no.2
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• pp.122-125
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• 2015

House dust mite (HDM) as a major allergen and damage-associated molecular pattern (DAMP) such as S100A8 and S100A9 trigger the pathogenesis and severity of allergic disease such as asthma. Regulation of neutrophil apoptosis is an important immune response and its dysregulation is involved in pathogenesis of allergic diseases. In this study, we examined the effects of HDM, S100A8 and S100A9 on spontaneous apoptosis of normal neutrophils. We considered the importance of the difference between in vitro and in vivo results and developed a new in vitro system consisting of a combination of immune cells and T helper (Th) cytokines. Extract of Dermatophagoides pteronyssinus (DP), S100A8, and S100A9 inhibited neutrophil apoptosis in culture of neutrophils alone without other leukocytes. DP and S100A8 more strongly suppressed neutrophil apoptosis in combinations of neutrophils, eosinophils, lymphocytes or monocytes than in a culture of neutrophils alone. Anti-apoptotic effect of S100A9 in the mixture of immune cells was similar to that in neutrophils. DP, S100A8, and S100A9 blocked neutrophil apoptosis, regardless of pretreatment with a T helper (Th) 1 cytokine (IFN-$\gamma$), Th2 cytokines (IL-4 and IL-10), a Th9 cytokine (IL-9), a Th17 cytokine (IL-17), a Treg-producing cytokine (TGF-$\beta$). These findings may enable elucidation of allergy pathogenesis due to HDM and DAMP.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.100-109
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• 2015

Controlling balance between T-helper type 1 (Th1) and T-helper type 2 (Th2) plays a pivotal role in maintaining the biological rhythm of Th1/Th2 and circumventing diseases caused by Th1/Th2 imbalance. Interleukin 4 (IL-4) is a Th2-type cytokine and often associated with hypersensitivity-related diseases such as atopic dermatitis and allergies when overexpressed. In this study, we have tried to elucidate the function of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (EC-18) as an essential modulator of Th1/Th2 balance. EC-18 has showed an inhibitory effect on the production of IL-4 in a dose-dependent manner. RT-PCR analysis has proved EC-18 affect the transcription of IL-4. By analyzing the phosphorylation status of Signal transducer and activator of transcription 6 (STAT6), which is a transcriptional activator of IL-4 expression, we discovered that EC-18 induced the decrease of STAT6 activity in several stimulated cell lines, which was also showed in STAT6 reporter analysis. Co-treatment of EC-18 significantly weakened atopy-like phenotypes in mice treated with an allergen. Collectively, our results suggest that EC-18 is a potent Th2 modulating factor by regulating the transcription of IL-4 via STAT6 modulation, and could be developed for immune-modulatory therapeutics.