• IMMUNE NETWORK
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• v.24 no.1
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• pp.6.1-6.17
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• 2024

The intricate role of innate type-2 cytokines in immune responses is increasingly acknowledged for its dual nature, encompassing both protective and pathogenic dimensions. Ranging from defense against parasitic infections to contributing to inflammatory diseases like asthma, fibrosis, and obesity, these cytokines intricately engage with various innate immune cells. This review meticulously explores the cellular origins of innate type-2 cytokines and their intricate interactions, shedding light on factors that amplify the innate type-2 response, including TSLP, IL-25, and IL-33. Recent advancements in therapeutic strategies, specifically the utilization of biologics targeting pivotal cytokines (IL-4, IL-5, and IL-13), are discussed, offering insights into both challenges and opportunities. Acknowledging the pivotal role of innate type-2 cytokines in orchestrating immune responses positions them as promising therapeutic targets. The evolving landscape of research and development in this field not only propels immunological knowledge forward but also holds the promise of more effective treatments in the future.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.11.1-11.26
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• 2022

When epithelial cells are exposed to potentially threatening external stimuli such as allergens, bacteria, viruses, and helminths, they instantly produce "alarmin" cytokines, namely, IL-33, IL-25, and TSLP. These alarmins alert the immune system about these threats, thereby mobilizing host immune defense mechanisms. Specifically, the alarmins strongly stimulate type-2 immune cells, including eosinophils, mast cells, dendritic cells, type-2 helper T cells, and type-2 innate lymphoid cells. Given that the alarm-raising role of IL-33, IL-25, and TSLP was first detected in allergic and infectious diseases, most studies on alarmins focus on their role in these diseases. However, recent studies suggest that alarmins also have a broad range of effector functions in other pathological conditions, including psoriasis, multiple sclerosis, and cancer. Therefore, this review provides an update on the epithelium-derived cytokines in both allergic and non-allergic diseases. We also review the progress of clinical trials on biological agents that target the alarmins and discuss the therapeutic potential of these agents in non-allergic diseases.

• Journal of Life Science
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• v.20 no.4
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• pp.503-510
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• 2010

Most allergens have protease activities, suggesting that proteases may be a key link between Th2-type immune reactions in allergic responses. Protease activated receptor (PAR) 2 is activated via the proteolytic cleavage of its N-terminal domain by proteinases. To know the role of PAR2 in Aspergillus protease allergen activated Th2 immune responses in airway epithelial cells, we investigated and compared immune cell recruitment and level of chemokines and cytokines between PAR2 knock out (KO) mice and wild type (WT) mice. There were evident immune cell infiltrations into the bronchial alveolar lavage fluid (BALF) of WT mice, but the infiltrations in PAR2 KO mice were significantly lowered than those of WT mice. The IL-25, TSLP, and eotaxin gene expressions were profoundly increased after Aspergillus protease, but their expression was significantly lowered in PAR2 KO mice in this study. Compared to PAR2 KO mice, OVA specific IgE concentrations in serum of WT mice were quite increased; moreover, the IgE level of PAR2 KO mice was lower than in WT mice. The IL-25 expression by Aspergillus protease stimulation was significantly reduced by p38 specific inhibitor treatment. In this study, we determined that Th2 response was initiated with IL-25 and TSLP mRNA up-regulation in lung epithelial cells via PAR2 after Aspergillus protease allergen treatment.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.43 no.2
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• pp.137-147
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• 2017

The human skin is an ecosystem that provides habitat to various microorganisms. These comprise the skin microbiome and provide numerous benefits in addition to maintaining a symbiotic relation with the host. Various metabolites generated by the skin microbiome exert beneficial effects such as strengthening the skin barrier, and anti-aging and anti-inflammatory functions. In this study, we isolated a novel bacterium, designated Sporichthyacae strain K-07, from the human skin. Analysis of 16S rRNA gene sequences showed that the newly found bacterium shares 93.4% homology with the genus Sporichthya, thus corroborating the discovery of a novel genus. We further analyzed the effect of the novel strain in vitro, by treating HaCaT cells with bacterial metabolite products. Treatment resulted in changes in the mRNA expression levels of filaggrin, claudin1, claudin4, SMase, CERS3, HAS3, aquaporin3, IL-6, TNF-${\alpha}$, TSLP, and TARC. Specifically, the levels of filaggrin, claudin1, claudin4, SMase, CERS3, HAS3, and aquaporin3 were higher in strain K-07 metabolite product-treated cells than in control cells. These results showed that metabolite products of the novel strain K-07 enhanced the skin barrier and exert anti-inflammatory effects. Therefore, these metabolite products could be potentially used for treatment of skin conditions.

• Toxicological Research
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• v.28 no.3
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• pp.159-164
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• 2012

Allergic skin inflammation such as atopic dermatitis (AD) is characterized by edema and infiltration with various inflammatory cells such as mast cells, basophils, eosinophils and T cells. Thymic stromal lymphopoietin (TSLP) is produced mainly by epidermal keratinocytes, as well as dermal fibroblasts and mast cells in the skin lesions of AD. Omega-3 polyunsaturated fatty acids in fish oil can reduce inflammation in allergic patients. Fermentation has a tremendous capacity to transform chemical structures. The antiinflammatory effects of fish oil have been described in many diseases, but the beneficial effects by which fermented olive flounder oil (FOF) modulates the allergic response is poorly understood. In this study, we produced FOF and tested its ability to suppress the various allergic inflammatory responses. The ability of FOF to modulate the immune system was investigated using a mouse model of AD. The FOF-treated group showed significantly decreased immunoglobulin E (IgE) and histamine in serum. Also, the increased TSLP expression was significantly inhibited in the FOF group; the FOF-treated group was not appreciably different from the hydrocort cream treatment group. In addition, FOF treatment resulted in a smaller spleen size with reduced the thickness and length compared to the induction group. Splenocytes from mice treated with FOF produced significantly less IFN-${\gamma}$, IL-4, T-box transcription factor (T-bet) and GATA binding protein 3 (GATA3) expression compared with the induction group. These results suggest that FOF may be effective in treating the allergic symptoms of AD. 5.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.32 no.2
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• pp.94-106
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• 2019

Objectives : This study was conducted to investigate the effects of Gwakhyangjeonggi-san(GJS) on atopic dermatitis(AD) induced by 2,4-dinitrochlorobenzene(DNCB) in mice. Methods : The mice(Balb/c mice) were divided into three groups; normal Balb/c mice with oil treatment(Sham group), DNCB-induced AD mice(AD group), and GJS treated AD mice(GJS group). GJS group were orally administered GJS daily for 2 weeks. We observed changes of clinical skin severity score, the expression of thymic stromal lymphopoietin(TSLP), interleukin(IL)-4 and tumor necrosis factor(TNF)-${\alpha}$ in skin and mast cell infiltration. Also, serum immunoglobulinE(IgE), IL-4, $TNF-{\alpha}$ and IL-6 were evaluated. Results : The clinical skin severity score of GJS group was decreased compared to AD group. In hematoxylin and eosin staining results, GJS group showed a significant reduction of epithelial skin thickness. In addition, expression of TSLP and mast cell infiltration in skin were also reduced by GJS treatment compared to those of AD group. Thus, we evaluated expression of IL-4, Th2-dependent cytokine, and $TNF-{\alpha}$, pro-inflammatory cytokine in skin. GJS significantly reduced both IL-4 and $TNF-{\alpha}$ compared to AD mice. Moreover, levels of IgE, IL-4, $TNF-{\alpha}$ and IL-6 in plasma also significantly decreased by oral GJS treatment. Conclusion : The present study suggests that GJS can significantly reduced symptoms of AD, therefore it can be a promising candidate for anti-atopic dermatitis treatment.

• Journal of Life Science
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• v.28 no.1
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• pp.17-25
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• 2018

In this study, we examined the efficacy of the immune regulation of ${\beta}$-1,3/1,6-glucan and Lactobacillus plantarum LM1004 on atopic dermatitis models. The oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 on mice significantly decreased the amount of scratching, leakage to evans blue, and concentrations of serum immunoglobulin E (IgE) and histamine compared with the atopic dermatitis - induced group. When atopic dermatitis was induced, the transcription factors (GATA-3, retinoic acid-related orphan receptor ${\gamma}$ T [$ROR{\gamma}T$]) and cytokines (interleukin-4 [IL-4], IL-17) of Th2 and Th17 cells were overexpressed at the transcriptional level, and they significantly decreased with oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004. In addition, ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 were shown to modulate the immune balance by increasing the expression of Th1 and Treg transcription (T-bet, forkhead box p3 [Foxp3]) and cytokines (interferon-${\gamma}$ [IFN-${\gamma}$], transforming growth factor-${\beta}$ [TGF-${\beta}$]). Galectin-9 and filaggrin were significantly lower in the atopic dermatitis - induced group and significantly higher in the ${\beta}$-1,3/1,6-glucan-treated group. In contrast, thymic stromal lymphopoietin (TSLP) was highest in the atopic dermatitis-induced group, while mice that were orally administered ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 showed similar TSLP levels to the control group. These results indicate that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 have immunomodulatory effects and atopic dermatitis improvement effects in an animal model of atopic dermatitis. Therefore, it is expected that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 can be used as natural materials in the treatment of atopic dermatitis.

• Journal of IKEEE
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• v.22 no.3
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• pp.842-845
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• 2018

In this paper, we propose low-power operational methods for thermal-energy-harvesting sensor circuits. Here, the amount of harvested current has been measured as low as 8uA. However the DC power consumption of the sensor circuit is known to consume much larger than 8uA. Thus, We propose the hardware-based power gating and software-based active/sleep timing control schemes, respectively, for controlling the power consumption of sensor circuit. In the hardware-based power gating scheme, if the ratio of Toff/Ton is larger than 22, the sensor can consume less than 8uA. For the software-based active/sleep control scheme, if the ratio of Tslp/Tact is larger than 3, we can suppress the current consumption below 8uA. The hardware-based and software-based schemes proposed in this paper would be helpful in various applications of energy-harvesting sensor circuits, where the power consumption is limited by an amount of harvested energy.

• Journal of Life Science
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• v.27 no.5
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• pp.600-610
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• 2017

It was common that the classification of itching was classified into four categories according to the neurophysiological mechanisms of pruritoceptive itching, neuropathic itching, neurogenic itching and psychogenic itching. Recently it was classified by clinical criteria. The neurotransmission pathway of itch is divided into histamine-dependent pathway and histamine-independent pathway. Different receptors and neuropeptides act on each itch mediator. Itch mediators such as histamine, BAM8-22, and chloroquine are transmitted through the histamine-dependent pathway. Cowhage spicule, protease, and TSLP (Thymic stromal lymphopoietin) have been reported to be related to the histamine-independent pathway. These itch mediators, receptors, and neuropeptides are the targets of treatment for itching. Although itching and pain are typical noxious stimuli, and in the past, it was argued that two senses were transmitted through one noxious stimulus receptor. It has recently been shown that itching and pain have an independent neurotransmitter system and both neuronal systems inhibit each other. In addition, the mutual antagonism between itching and pain is explained by various mechanisms. Recently, many new mediators and receptors are being studied. The studies on histamine 4 receptor (H4 receptor) have been actively conducted. And the H4 receptors are expressed in immune cells such as T cells. The therapeutic agent for blocking the H4 receptor can inhibit the inflammatory reaction itself, which is important for the itching and chronicization. Understanding the underlying mechanisms of itching and studying new itch mediators will lead to the development of effective therapies, and this is what I think the itching study will go on.

• Journal of Life Science
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• v.27 no.4
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• pp.482-499
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• 2017

Allergic diseases have increased over the past several decade worldwide including developing countries. Allergic inflammatory responses are caused by Th (T helper)2 immune responses, triggered by allergen ingestion by antigen presenting cells such as dendritic cells (DCs). Intestinal microorganisms control the metabolism and physiological functions of the host, contribute to early immune system maturation during the early life, and homeostasis and epithelial integrity during life. Bifidobacteria have strain-specific immunostimulatory properties in the Th1/Th2 balance, inhibit TSLP (thymic stromal lymphopoietin) and IgE expression, and promote Flg (Filaggrin) and FoxP3 (Treg) expression to alleviate allergies. In addition, unmethylated CpG motif ODN (oligodeoxynucleotides) is recognized by TLR (toll-like receptors)9 of B cells and plasmacytoid dendritic cells (pDCs) to induce innate and adaptive immune responses, while the butyrate produced by Clostridium butyricum activates the GPR (G-protein coupled receptors)109a signaling pathway to induce the expression of anti-inflammatory gene of pDCs, and directly stimulates the proliferation of thymically derived regulatory T (tTreg) cells through the activation of GPR43 or inhibits the activity of HADC (histone deacetylase) to differentiate naive $CD4^+$ T cells into pTreg cells through the histone H3 acetylation of Foxp3 gene intronic enhancer.