• Allergy, Asthma & Immunology Research
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• 제10권6호
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• pp.662-674
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• 2018

Purpose: Group 2 innate lymphoid cells (ILC2s) have been implicated in the pathogenesis of allergic disease. However, the effect of allergen-specific immunotherapy (AIT) on ILCs remains to be clarified. The aim of this study was to evaluate the levels of ILC subsets in allergic rhinitis (AR) patients in response to house dust mite (HDM)-specific immunotherapy. Methods: We enrolled 37 AR patients undergoing AIT (16 responders and 11 non-responders) for 2 years, 35 HDM AR patients and 28 healthy subjects. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to identify ILC subsets. Stimulation of ILC2s with recombinant allergen-specific protein was used to determine ILC2's activation (CD69 expression). Results: Responder AIT patients and healthy subjects had a decreased frequency of circulating ILC2s compared to non-responder AIT and AR patients. Conversely, ILC1s from responder AIT patients and healthy subjects showed increased frequency compared to non-responder AIT and AR patients. The frequency of ILC3s natural cytotoxicity receptor $(NCR)^+$ and $NCR^-$ in responder AIT patients was significantly lower compared to AR patients and healthy subjects. The ILC1: ILC2 proportion in responder AIT patients was similar to that of healthy subjects. PBMCs from patients who were responders to AIT had a significantly lower expression of the activation marker CD69 on ILC2s in response to allergen re-stimulation compared to AR patients, but no difference compared to non-responder AIT patients and healthy subjects. Conclusions: We propose that AIT might affect ILC responses. The activation of ILC2s was reduced in AR patients treated with AIT. Our results indicate that a relative ILC1/ILC2 skewed response is a possible key to successful AIT.

• Clinical and Experimental Reproductive Medicine
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• 제45권4호
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• pp.154-162
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• 2018

Objective: The fallopian tubes play a critical role in the early events of fertilization. The rapid innate immune defense is an important part of the fallopian tubes. Toll-like receptor 3 (TLR3), as a part of the innate immune system, plays an important role in detecting viral infections. In this basic and experimental study, the effect of sex hormones on the function of TLR3 in the OE-E6/E7 cell line was investigated. Methods: The functionality of TLR3 in this cell line was evaluated by cytokine measurements (interleukin [IL]-6 and IL-1b) and the effects of sex hormones on TLR3 were tested by an enzyme-linked immunosorbent assay kit. Additionally, TLR3 small interfering RNA (siRNA) and a TLR3 function-blocking antibody were used to confirm our findings. Results: The production of IL-6 significantly increased in the presence of polyinosinic-polycytidylic acid (poly(I:C)) as the TLR3 ligand. Using a TLR3-siRNA-ransfected OE-E6/E7 cell line and function-blocking antibody confirmed that cytokine production was due to TLR3. In addition, 17-${\beta}$ estradiol and progesterone suppressed the production of IL-6 in the presence and absence of poly(I:C). Conclusion: These results imply that sex hormones exerted a suppressive effect on the function of TLR3 in the fallopian tube cell line when different concentrations of sex hormones were present. The current results also suggest that estrogen receptor beta and nuclear progesterone receptor B are likely to mediate the hormonal regulation of TLR3, as these two receptors are the main estrogen and progesterone receptors in OEE6/E7 cell line.

• 한국수산과학회지
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• 제55권3호
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• pp.379-385
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• 2022

This study was conducted to evaluate the dietary supplementation of citrus byproduct (CBP) on the growth performance, feed utilization, and innate immune responses of juvenile olive flounder Paralichthys olivaceus under low water temperatures (11-15℃). Dietary L-ascorbyl-2-polyphosphate was replaced with graded CBP levels at 0 (Con), 25 (CBP25), 50 (CBP50), 75 (CBP75), and 100% (CBP100). Triplicate groups of juvenile olive flounder were handfed with one of the diets twice a day for 42 days. The growth performance and feed utilization of fish fed with diet containing levels of CBP75 or CBP100 increased significantly compared to those of fish with fed Con. Dietary CBP supplementation increased the protein efficiency ratio in fish. There was no significant differences in innate immune responses between groups, even though CBP supplementation tended to increase. These findings indicate that CBP could be used as a vitamin C source and improve the growth performance of juvenile olive flounder under low water temperatures.

• Molecules and Cells
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• 제45권10호
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• pp.702-717
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• 2022

Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulates beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediates protein interplay between NS5A and IKKε, thereby contributing to NS5A mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.

• IMMUNE NETWORK
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• 제23권4호
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• pp.31.1-31.18
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• 2023

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

• IMMUNE NETWORK
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• 제22권3호
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• pp.22.1-22.25
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• 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

• 대한수의사회지
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• 제48권3호
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• pp.177-191
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• 2012

2011년도 Nobel 생리(生理) 의학상(醫學賞) : 자연(自然)(선천)(先天) 면역(免疫)(innate immunity)의 활성화에 관한 연구업적으로 B. A. Beutler와 J. A. Hoffmann, 그리고 수지상세포(樹枝狀細胞)(dendritic cell; DC)발견과 적응(適應)(획득)(獲得)면역(免疫)(adaptive immunity)에 있어서의 그들 세포의 역할을 밝혀낸 R. M. Steinman의 공동수상으로 금년도 Nobel 생리 의학상 수상자가 결정되었다는 보도가 지난 10월 3일 있었다(1-3). 그들의 업적을 요약하면 대략 다음과 같다. (Steinman교수는 Nobel수상자 발표 3일전인 9월 30일 암으로 사망함). 그들은 면역기구(immune system)의 활성화의 관건(key)이 되는 원리를 밝혀냄으로써, 면역기구에 관한 우리들의 이해를 혁신하였던 것이다. 과학자들은 오랫동안 세균(bacteria)이나 기타 미생물병원체들에 의한 공격에 대비하여 그들 자신을 방어하는 사람이나 기타 동물체에서의 면역응답(免疫應答)(immune response)의 문지기들을 탐색해 왔다. Beutler와 Hoffmann은 그와 같은 병원미생물을 인식하여 생체의 면역응답의 첫 단계인 자연면역을 활성화 할 수 있는 수용체 단백질(toll-like receptor protein)을 규명한 것이다(4,5). 한편 Steinmann은 면역계의 수지상세포(DC)와 병원미생물이 생체로부터 배제되는 면역응답의 후기단계인 적응면역을 활성화하고 조절하는 그들의 독특한 재능을 규명해 낸 것이다(6-8). 그들 3명의 발명은, 면역응답의 자연 및 적응 양상(樣相)이 어떻게 활성화되는 가를 밝혀냄으로써 질병의 기전에 관한 참신한 식견(識見)을 제공한 것이다. 그들의 연구는 감염병(感染病)(infectious disease), 암(癌)(cancer) 그리고 염증성질환(炎症性疾患)(inflammatory disease)에 대응하는 예방과 치료의 개발을 위한 새로운 방법을 개척한 것이다.

• 대한암한의학회지
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• 제10권1호
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• pp.75-86
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• 2005

Disease associated with microorganisms are far from resolved by current therapeutics. One of effective approach to health maintenance and disease control is the use of dietary bacterial and carbohydrate supplements. This comprises use of probiotics and prebiotics. Probiotics mean the live microorganisms, which when administered in adequate amounts confer a health benefit on the host. Prebiotics mean a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria that can Improve the host health. Especially, probiotics has the relation which is close with innate immunity and adaptive immunity. And probiotics has the clinical value with many disease like lactose intolerance, constipation, acute gastroenteritis, food hypersensitivity and allergy, atopic dermatitis, crohn's disease, rheumatoid arthritis, pelvic radiotherapy, intestinal inflammation and chemical exposure, colon cancer, inhibitory effect of Helicobacter pylori and lowering the level of cholesterol. We use jointly korean medicine and probiotics and it has the more therapeutic effect in the many disease.

• KSBB Journal
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• 제25권6호
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• pp.497-506
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• 2010

Vaccine is a protective clinical measure capable of persuading immune system against infectious agents. Vaccine can be categorized as live attenuated and inactivated. Live attenuated vaccines activate immunity similar to natural infection by replicating living organisms whereas inactivated vaccines are either whole cell vaccines, eliciting immune response by killed organisms,or subunit vaccines, stimulating immunity by non-replicating sub cellular parts. The components of vaccine play a critical role in deciding the immune response mediated by the vaccine. The innate immune responds against the antigen component. Adjuvants represent an importantcomponent of vaccine for enhancing the immunogenicity of the antigens. Subunit vaccines with isolated fractions of killed and recombinant antigens are mostly co-administered with adjuvants. The delivery system of the vaccine is another essential component to ensurethat vaccine is delivered to the right target with right dosage form. Furthermore, vaccine delivery system ensures that the desired immune response is achieved by manipulating the optimal interaction of vaccine and adjuvantwith the immune cell. The aforementioned components along with routes of administration of vaccine are the key elements of a successful vaccination procedure. Vaccines can be administered either orally or by parenteral routes. Many groups had made remarkable efforts for the development of new vaccine and delivery system. The emergence of new vaccine delivery system may lead to pursue the immunization goals with better clinical practices.

• Clinical and Experimental Reproductive Medicine
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• 제38권3호
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• pp.119-125
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• 2011

Implantation of an embryo occurs during the mid-secretory phase of the menstrual cycle, known as the "implantation window." During this implantation period, there are significant morphologic and functional changes in the endometrium, which is followed by decidualization. Many immune cells, such as dendritic and natural killer (NK) cells, increase in number in this period and early pregnancy. Recent works have revealed that antigen-presenting cells (APCs) and NK cells are involved in vascular remodeling of spiral arteries in the decidua and lack of APCs leads to failure of pregnancy. Paternal and fetal antigens may play a role in the induction of immune tolerance during pregnancy. A balance between effectors (i.e., innate immunity and helper T [Th] 1 and Th17 immunity) and regulators (Th2 cells, regulatory T cells, etc.) is essential for establishment and maintenance of pregnancy. The highly complicated endocrine-immune network works in decidualization of the endometrium and at the fetomaternal interface. We will discuss the role of immune cells in the implantation period and during early pregnancy.