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Toll-like receptor 9 is involved in the induction of galectin-9 protein by dietary anti-allergic compound fucoidan toll样受体9参与饮食抗过敏化合物岩藻糖丹诱导半乳糖凝集素-9蛋白
IF 0.7 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.3934/allergy.2023002
G. Ezan, M. Mizuno
Dietary intervention of fucoidan extracted from Saccharina japonica brown seaweed has been ascertained to favor an increase of galectin-9 protein in the intestine of allergic mice, resulting in the attenuation of the food allergy symptoms. The molecular mechanism underpinning that galectin-9 secretion remains unclear. Recently, some evidence has suggested an implication of Toll-like receptor 9 (TLR9) in galectin-9 secretion. However, no investigation has been done. For this study, we aimed to understand the relationship between galectin-9 production and fucoidan intake, which will improve the therapeutic use of fucoidan in allergy treatment. Intestinal epithelial cells (IECs) were cultured in solid or transwell plates and apically exposed to fucoidan solutions and/or synthetic TLR9 agonist (CpG-ODN). The transcriptional response of the cells to galectin-9 (lgals9) and the TLR9 gene was evaluated by using q-RTPCR, and the protein expression of galectin-9 was analyzed by conducting an ELISA test. Knockdown of TLR9 in IECs was performed by targeting TLR9 siRNA, and its effect on galectin-9 release was assessed. We found that the interaction of fucoidan and IECs resulted in the upregulation of galectin-9 released in a dose- and time-dependent manner. The increase was further potentiated in combination with the TLR9 agonist. Fucoidan exposure to IECs tended to increase the mRNA expression of TLR9 in a way similar to that of the TLR9 agonist effect, and knockdown of TLR9 in IECs resulted in a decreased tendency of fucoidan-induced galectin-9 protein. TLR9 activation is therefore involved in the increased release of galectin-9 protein observed in IECs upon fucoidan exposure.
从日本褐藻中提取岩藻糖聚糖的饮食干预已被确定有利于过敏小鼠肠道中半乳糖凝集素-9蛋白的增加,从而减轻食物过敏症状。半乳糖凝集素-9分泌的分子机制尚不清楚。近年来,一些证据表明toll样受体9 (TLR9)在半乳糖凝集素-9分泌中的作用。然而,没有进行任何调查。在这项研究中,我们旨在了解半乳糖凝集素-9的产生与岩藻糖聚糖摄入量之间的关系,这将改善岩藻糖聚糖在过敏治疗中的治疗应用。肠上皮细胞(IECs)在固体或透孔板中培养,顶端暴露于岩藻聚糖溶液和/或合成TLR9激动剂(CpG-ODN)。采用q-RTPCR检测细胞对半乳糖凝集素-9 (lgals9)和TLR9基因的转录反应,ELISA检测半乳糖凝集素-9的蛋白表达。通过靶向TLR9 siRNA,在IECs中进行TLR9的敲低,并评估其对半乳糖凝集素-9释放的影响。我们发现岩藻聚糖和IECs的相互作用导致半乳糖凝集素-9以剂量和时间依赖性的方式释放上调。与TLR9激动剂联合使用时,这种增加进一步增强。岩藻多糖暴露于IECs后,与TLR9激动剂作用类似,有增加TLR9 mRNA表达的趋势,在IECs中,敲低TLR9导致岩藻多糖诱导的半凝集素-9蛋白有降低的趋势。因此,在岩藻聚糖暴露后,在iec中观察到,TLR9的激活与半乳糖凝集素-9蛋白释放增加有关。
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引用次数: 0
Aging and immunity: Unraveling the complex relationship 衰老与免疫:揭开复杂关系
Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.3934/allergy.2023015
Arosh S. Perera Molligoda Arachchige

The process of aging is an inherent facet of human existence, entailing various changes within the body, notably in the immune system. This article explores the profound impact of aging on immunity, elucidating its implications for healthcare, disease vulnerability and overall quality of life. Drawing inspiration from the “Aging and Immunity” special issue of AIMS Allergy and Immunology, this commentary provides a comprehensive perspective on the intricate interplay between aging and immunity. The immune system, a complex shield against pathogens, undergoes a decline in efficacy as individuals age, known as immunosenescence. This decline encompasses reduced immune cell production and communication, rendering older individuals more susceptible to infections and less responsive to vaccines. Additionally, chronic low-grade inflammation, termed inflammaging, emerges as a hallmark of aging and immune system alteration, contributing to age-related diseases. Recent research underscores the connection between the gut microbiota and immune aging, raising the prospect of interventions targeting gut health to enhance immunity in older individuals. Strategies for fortifying immunity in aging populations encompass optimized vaccination approaches, lifestyle modifications, anti-inflammatory interventions, targeted therapies and microbiota-based interventions. Addressing the challenges of aging and immunity necessitates collaborative efforts from policymakers, healthcare providers, researchers and communities, emphasizing healthy aging promotion, evidence-based interventions and equitable healthcare access. By delving into the multifaceted relationship between aging and immunity, this discourse envisions a future where research-driven advancements and holistic public health measures converge to enhance the well-being and resilience of older adults worldwide.

& lt; abstract>衰老的过程是人类生存的一个固有方面,涉及身体的各种变化,特别是免疫系统的变化。本文探讨了衰老对免疫的深刻影响,阐明了其对医疗保健、疾病易感性和整体生活质量的影响。从AIMS变态反应与免疫学杂志的“衰老与免疫”特刊中获得灵感,本评论对衰老与免疫之间错综复杂的相互作用提供了一个全面的视角。免疫系统是抵御病原体的复杂屏障,随着个体年龄的增长,其效力会下降,这被称为免疫衰老。这种下降包括免疫细胞产生和通讯减少,使老年人更容易受到感染,对疫苗的反应更差。此外,慢性低度炎症,被称为<italic> inflaming</italic>,是衰老和免疫系统改变的标志,导致与年龄相关的疾病。最近的研究强调了肠道微生物群与免疫衰老之间的联系,提出了针对肠道健康的干预措施以增强老年人免疫力的前景。加强老年人群免疫力的策略包括优化疫苗接种方法、改变生活方式、抗炎干预、靶向治疗和基于微生物群的干预。应对老龄化和免疫的挑战需要决策者、卫生保健提供者、研究人员和社区的共同努力,强调促进健康老龄化、循证干预和公平获得卫生保健。通过深入研究衰老与免疫之间的多方面关系,本文设想了一个未来,即研究驱动的进步和整体公共卫生措施相结合,以增强全球老年人的福祉和复原力。& lt; / abstract>
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引用次数: 0
Epigenetic regulation of the COVID-19 pathogenesis: its impact on the host immune response and disease progression COVID-19发病机制的表观遗传调控:对宿主免疫反应和疾病进展的影响
IF 0.7 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.3934/allergy.2023005
Zinia Pervin, Anika Tasnim, Hasib Ahamed, Md Al Hasibuzzaman
Coronavirus disease 2019 (COVID-19) is highly infectious and may induce epigenetic alteration of the host immune system. Understanding the role of epigenetic mechanisms in COVID-19 infection is a clinical need to minimize critical illness and widespread transmission. The susceptibility to infection and progression of COVID-19 varies from person to person; pathophysiology substantially depends on epigenetic changes in the immune system and preexisting health conditions. Recent experimental and epidemiological studies have revealed the method of transmission and clinical presentation related to COVID-19 pathogenesis, however, the underlying pathology of variation in the severity of infection remains questionable. Epigenetic changes may also be responsible factors for multisystem association and deadly systemic complications of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients. Commonly, epigenetic changes are evoked by alteration of the host's immune response, stress, preexisting condition, oxidative stress response, external behavioral or environmental factors, and age. In addition, the viral infection itself might manipulate the host immune responses associated with inflammation by reprogramming epigenetic processes which are the susceptible factor for disease severity and death. As a result, epigenetic events such as histone modification and DNA methylation are implicated in regulating pro-inflammatory cytokines production by remodeling macrophage and T-cell activity towards inflammation, consequently, may also affect tissue repair and injury resolution process. This review aims to discuss the comprehensive understanding of the epigenetic landscape of COVID-19 disease progression that varies from person to person with supporting interdisciplinary prognosis protocol to overcome systemic impairment.
2019冠状病毒病(COVID-19)具有高度传染性,并可能诱发宿主免疫系统的表观遗传改变。了解表观遗传机制在COVID-19感染中的作用是临床需要,以尽量减少危重疾病和广泛传播。对COVID-19感染和进展的易感性因人而异;病理生理学基本上取决于免疫系统的表观遗传变化和先前存在的健康状况。最近的实验和流行病学研究已经揭示了与COVID-19发病机制相关的传播方式和临床表现,但感染严重程度变化的潜在病理仍存在疑问。表观遗传变化也可能是严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)感染患者多系统关联和致命性全身并发症的主要因素。通常,表观遗传改变是由宿主的免疫反应、应激、既往状况、氧化应激反应、外部行为或环境因素以及年龄的改变引起的。此外,病毒感染本身可能通过重编程表观遗传过程来操纵与炎症相关的宿主免疫反应,而表观遗传过程是疾病严重程度和死亡的易感因素。因此,组蛋白修饰和DNA甲基化等表观遗传事件涉及通过重塑巨噬细胞和t细胞对炎症的活性来调节促炎细胞因子的产生,因此,也可能影响组织修复和损伤消退过程。本综述旨在讨论对COVID-19疾病进展的表观遗传学景观的全面理解,该景观因人而异,并支持跨学科预后方案,以克服系统性损害。
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引用次数: 0
The journey so far with SARS-CoV-2 variants: Pathogenesis, immunity and treatments SARS-CoV-2变体的历程:发病机制、免疫和治疗
Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.3934/allergy.2023016
Daniel Danladi Gaiya, Jonathan Danladi Gaiya, Richard Auta, Aliyu Muhammad, Bege Jonathan, Stella Kuyet Udu, Ekpa Emmanuel, Amina Shehu Bature

The recruitment of therapeutics and most importantly COVID-19 vaccines has seen a measurable reduction in transmission, re-infection, severity, hospitalization and mortality associated with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The development and approval of some vaccines and therapeutics undoubtedly signaled renewed hope for public health personnel, the government, the World Health Organization (WHO) and the entire world population. At present, most countries have progressed beyond administering first and second doses to administering COVID-19 vaccine updated boosters to prevent transmission and provide protection. Notably, a bivalent COVID-19 vaccine from Pfizer–BioNTech and Moderna, also called an “updated” COVID-19 vaccine booster dose, is a formulation that houses the original virus strain and omicron BA.1, which provides broad immunity against COVID-19 including the omicron variant (BA.1) and the Paxlovid drug (Nirmatrelvir-ritonavir) authorized for use by the Food and Drug Administration (FDA) and the European Medicines Agency. This current review outlines the variant of concern (VOC), viral cell entry and pathogenesis, host immunity and viral immune evasion. In addition, we discuss the therapeutic and vaccine treatment approach, WHO and FDA authorization, vaccine storage and vaccine efficacy. In conclusion, bearing in mind the trend of continued mutations as observed on the spike (S) glycoprotein and receptor binding domain (RBD) of SARS-CoV-2, which lead to more immune-evasive strains such as BQ.1, BQ.1.1, BF.7, XBB and XBB.1, researcher and clinician attention should be tailored toward the design and development of variant-specific vaccines for future interventions.

& lt; abstract>通过使用治疗药物,最重要的是COVID-19疫苗,与新型严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)相关的传播、再感染、严重程度、住院和死亡率显著降低。一些疫苗和疗法的开发和批准无疑标志着公共卫生人员、政府、世界卫生组织(世卫组织)和全世界人民重新燃起了希望。目前,大多数国家已从接种第一剂和第二剂发展到接种更新的COVID-19疫苗加强剂,以预防传播并提供保护。值得注意的是,辉瑞- biontech和Moderna合作开发的一种双价COVID-19疫苗,也被称为“更新版”COVID-19疫苗加强剂,是一种含有原始病毒株和组粒ba1的配方,可提供针对COVID-19的广泛免疫,包括组粒变体(ba1)和Paxlovid药物(Nirmatrelvir-ritonavir),已获得美国食品和药物管理局(FDA)和欧洲药品管理局(European Medicines Agency)的批准。本文综述了关注变异(VOC)、病毒细胞进入和发病机制、宿主免疫和病毒免疫逃避。此外,我们还讨论了治疗和疫苗治疗方法、WHO和FDA授权、疫苗储存和疫苗功效。总之,考虑到在SARS-CoV-2的刺突(S)糖蛋白和受体结合域(RBD)上观察到的持续突变趋势,导致更多的免疫逃避菌株,如BQ.1、BQ.1.1、BF.7、XBB和XBB.1,研究人员和临床医生应将注意力集中在设计和开发变异特异性疫苗上,以用于未来的干预措施。& lt; / abstract>
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引用次数: 0
Formulating preservatives to enhance stability of crude extracts of food allergens used for food allergy management and immunotherapy 配制防腐剂,以提高用于食物过敏管理和免疫治疗的食物过敏原粗提取物的稳定性
IF 0.7 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.3934/allergy.2023004
Rabia F Khan, Sheharbano Bhatti, Z. Abbas

Due to rapid degradation of food allergenic extracts, devising some optimal conditions is mandatory to boost shelf life of extracts for appropriate diagnosis of allergy and immunotherapy. In the current study, food extracts of Bos domesticus (cow) milk, Gallus domesticus (chicken) egg, Trititcum aestivum (wheat), Gallus domesticus (chicken) meat and Arachis hypogaea (peanut) were prepared and their protein estimation was evaluated by bicinchoninic acid (BCA) method. Stability of food extracts was evaluated under two groups of preservatives; storage with coca's solution (mixture of sodium chloride (NaCl) and sodium bicarbonate (NaHCO3)) and stabilizing buffer (sucrose and ethylene diamine tetra-acetic acid (EDTA)). Effect of cocktail of protease inhibitors ((phenyl methyl sulfonyl fluoride (PMSF) and dithiothreitol (DTT)) and glycerol was checked on food extracts under both groups of preservatives. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) was performed for food protein extracts after 1, 3 and 6 months under both conditions. Size of obtained protein bands were compared with allergen database (http://www.allergen.org) in order to check their potential allergenicity. Extracts stored with coca's solution remained more potent as compared to stabilizing buffer for up to 3 months except Gallus domesticus egg, whose proteins remained more potent in stabilizing buffer as compared to coca's solution. Most of the proteins deteriorated at 6 months of storage. Glycerol had shown better results under both conditions. A formulation containing a combination of coca's solution along with cocktail of protease inhibitors and glycerol improved the shelf life of food extracts for up to 3 months, showing better potential for stabilization of allergenic food extracts and their use for immunotherapy.

由于食品致敏提取物的快速降解,设计一些最佳条件是必要的,以提高提取物的保质期,以适当的诊断过敏和免疫治疗。本研究以牛(Bos domesticus)奶、鸡(Gallus domesticus)蛋、小麦(Trititcum aestivum)、鸡(Gallus domesticus)肉和花生(Arachis hypogaea)为原料制备食品提取物,并采用bicinchoninic acid (BCA)法对其进行蛋白质评价。在两组防腐剂的作用下,评价了食品提取物的稳定性;用古柯溶液(氯化钠和碳酸氢钠的混合物)和稳定缓冲液(蔗糖和乙二胺四乙酸(EDTA))储存。研究了蛋白酶抑制剂(苯基甲基磺酰氟(PMSF)和二硫苏糖醇(DTT))与甘油混合对两组防腐剂下食品提取物的影响。在两种条件下分别于1、3和6个月后对食品蛋白提取物进行十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS PAGE)。将获得的蛋白条带大小与过敏原数据库(http://www.allergen.org)进行比较,以检查其潜在的致敏性。与稳定缓冲液相比,用古柯溶液储存的提取物在长达3个月的时间里仍具有更强的效力,但家鸡蛋除外,其蛋白质在稳定缓冲液中仍比古柯溶液更强。大多数蛋白质在储存6个月后变质。甘油在两种条件下均表现出较好的效果。一种含有古柯溶液与蛋白酶抑制剂和甘油混合物的配方将食品提取物的保质期延长了3个月,显示出稳定致敏性食品提取物及其用于免疫治疗的更好潜力。
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引用次数: 0
Arachidonic acid metabolism and its use in the diagnosis of mastocytosis 花生四烯酸代谢及其在肥大细胞增多症诊断中的应用
IF 0.7 Q4 IMMUNOLOGY Pub Date : 2023-01-01 DOI: 10.3934/allergy.2023006
P. Jandus
Mast cells and basophils degranulate upon activation, releasing preformed mediators from intracellular granules into the extracellular environment, of which tryptase and histamine are the two most common and best characterized mediators. Despite the large number of mediators synthesized by mast cells, the non-tryptase biomarkers used to evaluate systemic mastocytosis and mast cell activation syndrome do not include the metabolites of the prestored amine histamine and the de novo synthesized phospholipids prostaglandin D2 and leukotriene C4. Currently, these markers are not used as criteria for the diagnosis of mastocytosis and mast cell activation syndrome. However, consensus groups foster the use of increases in measured baseline levels of these metabolites as potential diagnostic criteria. Metabolites of arachidonic acid such as prostaglandin D2 or leukotriene C4 play a role in the development of symptoms in systemic mastocytosis and mast cell activation syndrome. In this review, the metabolites of arachidonic acid and the detection of the metabolites of leukotrienes and prostaglandins in mastocytosis are highlighted. Measurement of these metabolites remains a major challenge because they are not widely available in daily clinical practice. However, new insights have been gained in recent years, and their application in the clinic has progressed.
肥大细胞和嗜碱性细胞在激活后会脱粒,从细胞内颗粒释放预先形成的介质到细胞外环境,其中胰蛋白酶和组胺是两种最常见和最具特征的介质。尽管肥大细胞合成了大量的介质,但用于评估全身肥大细胞增多症和肥大细胞活化综合征的非胰蛋白酶生物标志物不包括预先储存的胺组胺和新合成的磷脂前列腺素D2和白三烯C4的代谢物。目前,这些标志物尚未被用作肥大细胞增多症和肥大细胞激活综合征的诊断标准。然而,共识组提倡使用这些代谢物测量基线水平的增加作为潜在的诊断标准。花生四烯酸的代谢物如前列腺素D2或白三烯C4在全身性肥大细胞增多症和肥大细胞激活综合征的症状发展中发挥作用。本文就花生四烯酸代谢物、白三烯和前列腺素代谢物在肥大细胞增多症中的检测作一综述。这些代谢物的测量仍然是一个主要的挑战,因为它们在日常临床实践中没有广泛使用。然而,近年来获得了新的见解,并在临床中的应用取得了进展。
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引用次数: 0
Glucuronoxylomannan: the salient polysaccharide in cryptococcal immunity 葡萄糖醛酸甘露聚糖:隐球菌免疫中的显著多糖
IF 0.7 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.3934/allergy.2022008
Mansur Aliyu, A. Saboor-Yaraghi, S. Khodavaisy, Behrouz Robat-Jazi, Muhammad Ibrahim Getso
Cryptococcal meningitis (CM) is a dominant cause of morbidity and mortality among patients with human immunodeficiency virus/ acquired immune deficiency syndrome (HIV/AIDS) caused by Cryptococcus neoformans and Cryptococcus gattii species complex. The complex is composed of closely related members, yet with diverse epidemiology, pathogenesis, and drug-resistant pattern. Cell-mediated immunity is the strongest pillar in immunity to cryptococcosis, further worsening HIV/AIDS patients' scenario. Antifungal resistance and immune evasion again tilt the host-parasite balance in favor of the fungal pathogen. In this regard, researchers are actively challenged to discover immunotherapy and vaccine for CM, to produce specific treatment and prevention that will address CM conventional therapeutics failure. As the major capsular polysaccharide of the Cryptococcus, which is tightly linked to pathogenicity, immunogenicity, and immune evasion, the glucuronoxylomannan (GXM) is cardinally targeted for vaccine and immunotherapy development. Further, the amount of GXM shed in body fluids correlates with the disease severity. Herein, we reviewed the literature with the journey so far in line with GXM as the salient immunological target on cryptococcosis.
隐球菌性脑膜炎(CM)是由新型隐球菌和加蒂隐球菌复合物引起的人类免疫缺陷病毒/获得性免疫缺陷综合征(HIV/AIDS)患者发病和死亡的主要原因。该复合体由密切相关的成员组成,但具有不同的流行病学、发病机制和耐药模式。细胞介导的免疫是对隐球菌病免疫的最强支柱,进一步恶化了艾滋病毒/艾滋病患者的情况。抗真菌耐药性和免疫逃避再次使宿主-寄生虫的平衡倾向于真菌病原体。在这方面,研究人员面临着积极的挑战,以发现免疫疗法和疫苗,以产生特异性的治疗和预防,以解决CM传统治疗方法的失败。葡萄糖醛酸甘露聚糖(glucuronoxylomannan, GXM)是隐球菌的主要荚膜多糖,与致病性、免疫原性和免疫逃避密切相关,是疫苗和免疫治疗发展的重要靶点。此外,体液中GXM的含量与疾病的严重程度相关。在此,我们回顾了迄今为止的文献,一致认为GXM是隐球菌病的显着免疫靶点。
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引用次数: 0
The backfiring effect of fairness salience in health messages regarding food allergies and diabetes 在关于食物过敏和糖尿病的健康信息中突出公平的反作用
IF 0.7 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.3934/allergy.2022010
Melissa M Foster
Social media posts intended to increase empathy thereby garnering support for public policy that improves the health and well-being of vulnerable populations can make salient the fact that vulnerable populations' experiences are unfair. For example, children with food allergies or diabetes often do not have access to emergency medication and can be isolated and treated poorly by peers. Raising awareness of this disparity, especially when paired with an image of an afflicted child, was expected to increase empathy which could then drive improvements in healthcare policy. However, data from two experimental studies suggest that making injustice salient in such a persuasive appeal can backfire, having the opposite effect as intended. When injustice salience was paired with an image of a patient with food allergies or diabetes, participants, especially those who self-identify as politically conservative, felt less empathy and were less supportive of protective policies. This study seeks to understand the counterintuitive responses people have when presented with clear examples of disparities in conjunction with patient images.
社交媒体上旨在增加同理心,从而获得对改善弱势群体健康和福祉的公共政策的支持的帖子,可能会突出弱势群体的经历是不公平的这一事实。例如,患有食物过敏或糖尿病的儿童往往无法获得紧急药物,并且可能被同龄人隔离和虐待。提高对这一差距的认识,特别是当与受折磨的孩子的形象搭配在一起时,有望增加同情心,从而推动医疗保健政策的改善。然而,两项实验研究的数据表明,在这种有说服力的呼吁中突出不公正可能会适得其反,产生与预期相反的效果。当不公正现象与食物过敏或糖尿病患者的照片搭配在一起时,参与者,尤其是那些自认为在政治上保守的人,对保护政策的同情和支持程度会降低。本研究旨在了解人们在与患者图像一起呈现差异的明确例子时的反直觉反应。
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引用次数: 0
IL-17 signaling is regulated through intrinsic stability control of mRNA during inflammation 炎症过程中,IL-17信号通过mRNA的内在稳定性控制来调节
IF 0.7 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.3934/allergy.2022014
R. Muromoto, K. Oritani, T. Matsuda
Interleukin (IL)-17 is a proinflammatory cytokine mainly produced by immune cells, especially activated T-helper 17 cells, which contribute to chronic inflammatory and autoimmune diseases including psoriasis. Although the molecular mechanisms of transcription in IL-17-mediated signaling pathways are well established, post-transcriptional control remains to be elucidated. Notably, IL-17 regulates post-transcriptional modifications, which induce elevated levels of target inflammatory mRNAs. Regnase-1, an endoribonuclease and deubiquitinase, post-transcriptionally downregulates various IL-17-driven signaling pathways, including mRNA stability. The ACT1-TBK1/IKKϵ pathway and ARID5A were induced and activated by IL-17-stimulation, leading to the inhibition of inflammatory mRNA degradation by Regnase-1. In this review, we focus on IL-17-mediated mRNA stabilization of psoriasis-related IκB-ζ and provide novel therapeutic strategies for the treatment of Th17-mediated inflammation and autoimmunity.
白细胞介素(IL)-17是一种促炎细胞因子,主要由免疫细胞,特别是活化的t -辅助性17细胞产生,参与银屑病等慢性炎症和自身免疫性疾病的发生。尽管在il -17介导的信号通路中转录的分子机制已经建立,但转录后的控制仍有待阐明。值得注意的是,IL-17调节转录后修饰,诱导目标炎症mrna水平升高。regase -1,一种核糖核酸内切酶和去泛素酶,转录后下调各种il -17驱动的信号通路,包括mRNA的稳定性。il -17刺激可诱导和激活ACT1-TBK1/ ikkλ通路和ARID5A,从而抑制Regnase-1对炎症mRNA的降解。在这篇综述中,我们将重点关注il -17介导的银屑病相关i - κ b -ζ mRNA稳定,并为治疗th17介导的炎症和自身免疫提供新的治疗策略。
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引用次数: 0
Antibodies and infected monocytes and macrophages in COVID-19 patients COVID-19患者的抗体与感染单核细胞和巨噬细胞
IF 0.7 Q4 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.3934/allergy.2022007
D. Ricke
The SARS-CoV-2 virus causes the COVID-19 disease associated with over 6.2 million deaths globally. Multiple early indicators raised the potential risk of the SARS-CoV-2 virus infecting monocytes and macrophages via Fc-receptor antibody binding based on closely related beta coronaviruses. Antibody Fc-receptor infection of phagocytic monocytes and macrophages is one type of antibody dependent enhancement of disease. Increased COVID-19 severity correlated with early high antibody responses on initial infection for unvaccinated adults. Clinical evidence suggests that for moderate antibody titer levels, antibodies binding to SARS-CoV-2 may contribute to viral spread, cytokine dysregulation, and enhanced COVID-19 disease severity. Primary immune responses appear to have too low of antibody titer to significantly contribute to Fc-receptor uptake by monocytes and macrophages for COVID-19 patients. Very high antibody titers created by SARS-CoV-2 vaccines also appear to inhibit Fc-receptor uptake and infection of monocytes and macrophages; this inhibition appears to decrease as antibody titer levels decrease. Cross reactive antibodies to other coronaviruses or moderate levels of SARS-CoV-2 antibodies may be contributing to antibody dependent enhancement of disease in critical COVID-19 patients.
SARS-CoV-2病毒导致的COVID-19疾病与全球620多万人死亡有关。多个早期指标提高了SARS-CoV-2病毒通过基于密切相关的β冠状病毒的fc受体抗体结合感染单核细胞和巨噬细胞的潜在风险。吞噬单核细胞和巨噬细胞的抗体fc受体感染是一种抗体依赖性增强疾病。COVID-19严重程度的增加与未接种疫苗的成年人初次感染时的早期高抗体反应相关。临床证据表明,在中等抗体滴度水平下,与SARS-CoV-2结合的抗体可能导致病毒传播、细胞因子失调和COVID-19疾病严重程度增强。初级免疫反应的抗体滴度似乎过低,无法显著促进COVID-19患者单核细胞和巨噬细胞对fc受体的摄取。SARS-CoV-2疫苗产生的非常高的抗体滴度似乎也抑制了fc受体的摄取和单核细胞和巨噬细胞的感染;这种抑制作用似乎随着抗体滴度的降低而降低。针对其他冠状病毒的交叉反应性抗体或中等水平的SARS-CoV-2抗体可能有助于COVID-19危重患者的抗体依赖性疾病增强。
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AIMS Allergy and Immunology
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