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Need to know which MHCs protect against COVID? There's an App for that! 需要知道哪些MHC可以预防新冠肺炎吗?有一个应用程序!
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-28 DOI: 10.1111/imcb.12680
Matthew J Witney, Anthony W Purcell, David C Tscharke

In this article, we discuss the recent observation by Augusto et al. made using a novel mobile phone application-based COVID-19 Citizen Science Study that an HLA genetic variant, HLA-B*15:01, is associated with asymptomatic SARS-CoV-2 infection. To explain this association, Augusto et al. describe a cross-reactive memory CD8+ T-cell response in HLA-B*15:01+ SARS-CoV-2 unexposed individuals that retains high avidity for two structurally conserved epitopes found in SARS-CoV-2 and seasonal coronavirus strains. These observations provide an insight into potential molecular determinants that facilitate rapid, early clearance of virus.

在这篇文章中,我们讨论了Augusto等人最近的观察结果。使用一项基于新型手机应用程序的新冠肺炎公民科学研究得出,HLA基因变体HLA-B*15:01与无症状的SARS-CoV-2感染有关。为了解释这种关联,Augusto等人。描述了HLA-B*15:01+SARS-CoV-2未暴露个体中的交叉反应性记忆CD8+T细胞应答,其对在严重急性呼吸系统综合征冠状病毒2型和季节性冠状病毒株中发现的两个结构保守的表位保持高亲和力。这些观察结果提供了对促进病毒快速、早期清除的潜在分子决定因素的深入了解。
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引用次数: 0
Bede Morris: a perspective from an early PhD candidate Bede Morris:早期博士生的观点
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-23 DOI: 10.1111/imcb.12684
Trevor J Heath

Between 1953 and 1986, Bede Morris published 28 papers in the Journal, each of which elucidated aspects of the lymphatic system. Initially with rats at the Kanematsu Institute at Sydney Hospital under FC Courtice, and then at Australian National University with sheep and a succession of PhD students, Morris developed an impressive series of experimental approaches and understandings of the role of the lymphatic system in the physiology and immunology of the mammalian body. In this piece for the 100th anniversary of the Journal, we celebrate his contributions to immunological research.

1953年至1986年间,贝德·莫里斯在《华尔街日报》上发表了28篇论文,每一篇都阐述了淋巴系统的各个方面。Morris最初在FC Courtice旗下的悉尼医院Kanematsu研究所与大鼠合作,然后在澳大利亚国立大学与绵羊和一系列博士生合作,开发了一系列令人印象深刻的实验方法和对淋巴系统在哺乳动物身体生理学和免疫学中作用的理解。在这篇纪念《华尔街日报》100周年的文章中,我们庆祝他对免疫学研究的贡献。
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引用次数: 1
Kevin Lafferty and the lymphocyte costimulator: theory and practice in Canberra 凯文·拉弗蒂和淋巴细胞共刺激剂:堪培拉的理论与实践
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-23 DOI: 10.1111/imcb.12683
Philip D Hodgkin

Between 1969 and 1983 the lab of Kevin Lafferty in Canberra developed the concept of the T-cell “costimulator,” an essential second signal for activation. A great deal of the work appeared in this journal before it was known as Immunology & Cell Biology (ICB). As part of the 100-year anniversary of the journal, I offer a personal reflection on Kevin's legacy and impact.

1969年至1983年间,堪培拉的凯文·拉弗蒂(Kevin Lafferty)实验室提出了t细胞“共刺激器”的概念,这是激活t细胞的重要第二信号。在这本杂志被称为《免疫学》之前,很多研究都发表在这本杂志上。细胞生物学(ICB)。作为该杂志100周年纪念的一部分,我对凯文的遗产和影响提出了个人的反思。
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引用次数: 1
Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections 用于测量严重急性呼吸系统综合征冠状病毒2型感染中二聚体IgA抗体的血清学测定
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-18 DOI: 10.1111/imcb.12682
Zihui Wei, Fiona Angrisano, Emily M Eriksson, Ramin Mazhari, Huy Van, Shuning Zheng, Rob J Center, Irene Boo, James McMahon, Jillian Lau, Nicholas Kiernan-Walker, Shazia Ruybal-Pesántez, Ivo Mueller, Leanne J Robinson, David A Anderson, Heidi E Drummer

Current serological tests cannot differentiate between total immunoglobulin A (IgA) and dimeric IgA (dIgA) associated with mucosal immunity. Here, we describe two new assays, dIgA-ELISA and dIgA-multiplex bead assay (MBA), that utilize the preferential binding of dIgA to a chimeric form of secretory component, allowing the differentiation between dIgA and monomeric IgA. dIgA responses elicited through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were measured in (i) a longitudinal panel, consisting of 74 samples (n = 20 individuals) from hospitalized cases of coronavirus disease 2019 (COVID-19); (ii) a longitudinal panel, consisting of 96 samples (n = 10 individuals) from individuals with mild COVID-19; (iii) a cross-sectional panel with PCR-confirmed SARS-CoV-2 infection with mild COVID-19 (n = 199) and (iv) pre–COVID-19 samples (n = 200). The dIgA-ELISA and dIgA-MBA demonstrated a specificity for dIgA of 99% and 98.5%, respectively. Analysis of dIgA responses in the longitudinal panels revealed that 70% (ELISA) and 50% (MBA) of patients elicited a dIgA response by day 20 after PCR diagnosis with a SARS-CoV-2 infection. Individuals with mild COVID-19 displayed increased levels of dIgA within the first 3 weeks after diagnosis but responses appeared to be short lived, compared with sustained IgA levels. However, in samples from hospitalized patients with COVID-19 we observed high and sustained levels of dIgA, up to 245 days after PCR diagnosis. Our results suggest that severe COVID-19 infections are associated with sustained levels of plasma dIgA compared with mild cases.

目前的血清学测试无法区分与粘膜免疫相关的总免疫球蛋白A(IgA)和二聚体IgA(dIgA)。在这里,我们描述了两种新的检测方法,dIgA-ELISA和dIgA多重珠粒检测(MBA),它们利用dIgA与嵌合形式的分泌成分的优先结合,允许dIgA和单体IgA之间的分化。通过严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染引起的dIgA反应在(i)由74个样本组成的纵向小组中进行了测量(n = 20人)来自2019冠状病毒病(新冠肺炎)住院病例;(ii)纵向面板,由96个样品(n = 10个个体)来自患有轻度新冠肺炎的个体;(iii)具有PCR证实的患有轻度新冠肺炎的SARS-CoV-2感染的横断面小组(n = 199)和(iv)新冠肺炎前样本(n = 200)。dIgA-ELISA和dIgA-MBA对dIgA的特异性分别为99%和98.5%。对纵向面板中dIgA反应的分析显示,70%(ELISA)和50%(MBA)的患者在PCR诊断为严重急性呼吸系统综合征冠状病毒2型感染后第20天引发dIgA应答。患有轻度新冠肺炎的个体在前3天内表现出dIgA水平升高 诊断后数周,但与持续的IgA水平相比,反应似乎是短暂的。然而,在新冠肺炎住院患者的样本中,我们观察到dIgA的高水平和持续水平,高达245 在PCR诊断后几天。我们的研究结果表明,与轻度病例相比,严重的新冠肺炎感染与血浆dIgA的持续水平有关。
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引用次数: 1
Sleeping Beauty kit sets provide rapid and accessible generation of artificial antigen-presenting cells for natural killer cell expansion 睡美人成套试剂盒可快速生成人工抗原呈递细胞,用于自然杀伤细胞扩增
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-16 DOI: 10.1111/imcb.12679
Lachlan J Dobson, Sarah C Saunderson, Samuel WJ Smith-Bell, Alexander D McLellan

Artificial antigen-presenting cells (aAPCs) offer a cost effective and convenient tool for the expansion of chimeric antigen receptor (CAR)-bearing T cells and NK cells. aAPCs are particularly useful because of their ability to efficiently expand low-frequency antigen-reactive lymphocytes in bulk cultures. Commonly derived from the leukemic cell line K562, these aAPCs lack most major histocompatibility complex expression and are therefore useful for NK cell expansion without triggering allogeneic T-cell proliferation. To combat difficulties in accessing existing aAPC lines, while circumventing the iterative lentiviral gene transfers with antibody-mediated sorting required for the isolation of stable aAPC clones, we developed a single-step technique using Sleeping Beauty (SB)–based vectors with antibiotic selection options. Our SB vectors contain options of two to three genes encoding costimulatory molecules, membrane-bound cytokines as well as the presence of antibiotic-resistance genes that allow for stable transposition-based transfection of feeder cells. Transfection of K562 with SB vectors described in this study allows for the surface expression of CD86, 4-1BBL, membrane-bound (mb) interleukin (IL)-15 and mbIL-21 after simultaneous transposition and antibiotic selection using only two antibiotics. aAPCs successfully expanded NK cells to high purity (80–95%). Expanded NK cells could be further engineered by lentiviral CAR transduction. The multivector kit set is publicly available and will allow convenient and reproducible in-house production of effective aAPCs for the in vitro expansion of primary cells.

人工抗原呈递细胞(aAPC)为携带嵌合抗原受体(CAR)的T细胞和NK细胞的扩增提供了一种经济高效且方便的工具。aAPC特别有用,因为它们能够在大量培养物中有效扩增低频抗原反应性淋巴细胞。这些aAPC通常来源于白血病细胞系K562,缺乏大多数主要的组织相容性复合体表达,因此可用于NK细胞扩增,而不会引发同种异体T细胞增殖。为了克服获得现有aAPC系的困难,同时通过抗体介导的分选来避免重复的慢病毒基因转移,以分离稳定的aAPC克隆,我们使用具有抗生素选择选项的基于睡美人(SB)的载体开发了一种单步技术。我们的SB载体包含两到三个编码共刺激分子、膜结合细胞因子的基因,以及抗生素抗性基因的存在,这些基因允许稳定的基于转座的饲养细胞转染。本研究中描述的用SB载体转染K562,在同时转位和仅使用两种抗生素选择抗生素后,允许CD86、4-1BBL、膜结合(mb)白细胞介素(IL)-15和mbIL-21的表面表达。aAPC成功地将NK细胞扩增到高纯度(80-95%)。扩增的NK细胞可以通过慢病毒CAR转导进一步工程化。多载体试剂盒是公开的,可以方便且可重复地在内部生产有效的aAPC,用于原代细胞的体外扩增。
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引用次数: 0
Enhanced lupus progression in alcohol-administered Fc gamma receptor-IIb–deficiency lupus mice, partly through leaky gut-induced inflammation 酒精给予的Fc γ受体- iib缺乏性狼疮小鼠狼疮进展增强,部分通过漏性肠诱导炎症
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-14 DOI: 10.1111/imcb.12675
Wiwat Chancharoenthana, Supitcha Kamolratanakul, Phatcharapon Yiengwattananon, Pornpimol Phuengmaung, Kanyarat Udompornpitak, Wilasinee Saisorn, Pratsanee Hiengrach, Peerapat Visitchanakun, Marcus J Schultz, Asada Leelahavanichkul

Alcohol can induce a leaky gut, with translocation of microbial molecules from the gut into the blood circulation. Although the contribution of inflammation to organ-mediated damage in lupus has been previously demonstrated, the mechanistic roles of alcohol consumption in lupus activation are not known. Herein, we tested the effects of 10-week lasting alcohol administration on organ damages and immune responses in 8-week-old lupus-prone Fc gamma receptor IIb–deficient (FcγRIIb−/−) mice. Our study endpoints were evaluation of systemic inflammation and assessment of fecal dysbiosis along with endotoxemia. In comparison with alcohol-administered wild-type mice, FcγRIIb−/− mice demonstrated more prominent liver damage (enzyme, histological score, apoptosis, malondialdehyde oxidant) and serum interleukin(IL)-6 levels, despite a similarity in leaky gut (fluorescein isothiocyanate–dextran assay, endotoxemia and gut occludin-1 immunofluorescence), fecal dysbiosis (microbiome analysis) and endotoxemia. All alcohol-administered FcγRIIb−/− mice developed lupus-like characteristics (serum anti-dsDNA, proteinuria, serum creatinine and kidney injury score) with spleen apoptosis, whereas control FcγRIIb−/− mice showed only a subtle anti-dsDNA. Both alcohol and lipopolysaccharide (LPS) similarly impaired enterocyte integrity (transepithelial electrical resistance), and only LPS, but not alcohol, upregulated the IL-8 gene in Caco-2 cells. In macrophages, alcohol mildly activated supernatant cytokines (tumor necrosis factor-α and IL-6), but not M1 polarization–associated genes (IL-1β and iNOS), whereas LPS prominently induced both parameters (more prominent in FcγRIIb−/− macrophages than wild type). There was no synergy in LPS plus alcohol compared with LPS alone in both enterocytes and macrophages. In conclusion, alcohol might exacerbate lupus-like activity partly through a profound inflammation from the leaky gut in FcγRIIb−/− mice.

酒精会导致肠道渗漏,微生物分子从肠道转移到血液循环中。虽然炎症对狼疮中器官介导的损伤的贡献已经被证实,但饮酒在狼疮激活中的机制作用尚不清楚。在此,我们测试了持续10周的酒精给药对8周龄狼疮易感Fcγ受体iib缺陷(Fcγ riib−/−)小鼠器官损伤和免疫反应的影响。我们的研究终点是评估全身性炎症和评估粪便生态失调以及内毒素血症。与酒精给药的野生型小鼠相比,FcγRIIb - / -小鼠表现出更明显的肝损伤(酶、组织学评分、细胞凋亡、丙二醛氧化剂)和血清白细胞介素(IL)-6水平,尽管在漏肠(异硫氰酸酯-右糖酐荧光素测定、内毒素血症和肠道occludin-1免疫荧光)、粪便生态失调(微生物组分析)和内毒素血症方面相似。所有给予酒精的FcγRIIb−/−小鼠均表现出狼疮样特征(血清抗dsdna、蛋白尿、血清肌酐和肾损伤评分),并伴有脾脏凋亡,而对照FcγRIIb−/−小鼠仅表现出轻微的抗dsdna。酒精和脂多糖(LPS)同样会损害肠细胞的完整性(经上皮电阻),并且只有LPS而不是酒精上调Caco-2细胞中的IL-8基因。在巨噬细胞中,酒精轻度激活上清细胞因子(肿瘤坏死因子-α和IL-6),但不激活M1极化相关基因(IL-1β和iNOS),而LPS显著诱导这两个参数(在FcγRIIb−/−巨噬细胞中比野生型更明显)。在肠细胞和巨噬细胞中,与单独使用LPS相比,LPS加酒精没有协同作用。总之,酒精可能在一定程度上通过FcγRIIb−/−小鼠漏肠的深度炎症加剧狼疮样活动。
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引用次数: 1
The rising tide raises all ships 潮起潮落,百舸争流。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-14 DOI: 10.1111/imcb.12681
Samantha Le Sommer

It is easy to feel as if you are alone in academia, especially if you face challenges that not everyone does, or can, understand. Community is essential in facing these challenges, and we each have a role to play in creating a more equitable research community. Here, I discuss the importance of community, finding your village and being part of the academic support system.

在学术界,你很容易感到自己是孤独的,尤其是当你面临的挑战不是每个人都能理解,也不是每个人都能理解的时候。在面对这些挑战时,社区是必不可少的,我们每个人都可以发挥作用,创建一个更加公平的研究社区。在此,我将讨论社区的重要性、找到自己的村庄以及成为学术支持系统的一员。
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引用次数: 0
The seductive allure of spatial biology: accelerating new discoveries in the life sciences 空间生物学的诱人魅力:加速生命科学的新发现
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-12 DOI: 10.1111/imcb.12669
Arutha Kulasinghe, Fiona Wood, Gabrielle Belz

Spatial biology is a rapidly developing field which enables the visualization of protein and transcriptomic data while preserving tissue context and architecture. Initially used in discovery, there is growing promise for translational and diagnostic assay developments. Immediate applications are in precision medicine, such as being able to match patients to optimal therapies through better understanding the tumor microenvironment. However, it also has ramifications for many other disciplines (e.g. immunology, cancer, infectious disease and digital pathology). With increasingly massive data sets being generated, data storage, curation, analysis and sharing require more computational approaches and artificial intelligence–powered tools to fully utilize spatial tools. Here, we discuss spatial biology as an important convergent science approach to tackling complex global challenges in areas such as health.

空间生物学是一个快速发展的领域,它能够在保留组织背景和结构的同时实现蛋白质和转录组数据的可视化。最初用于发现,对转化和诊断分析的发展前景越来越大。直接应用于精准医学,例如通过更好地了解肿瘤微环境,使患者获得最佳治疗。然而,它也对许多其他学科(如免疫学、癌症、传染病和数字病理学)产生了影响。随着越来越多的海量数据集的生成,数据存储、管理、分析和共享需要更多的计算方法和人工智能工具来充分利用空间工具。在这里,我们讨论了空间生物学作为一种重要的融合科学方法,以应对健康等领域的复杂全球挑战。
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引用次数: 0
PE_PGRS45 (Rv2615c) protein of Mycobacterium tuberculosis perturbs mitochondria of macrophages 结核分枝杆菌PE_PGRS45(Rv2615c)蛋白干扰巨噬细胞线粒体
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-11 DOI: 10.1111/imcb.12677
Medha, ? Priyanka, Sadhna Sharma, Monika Sharma, ? Medha

The PE_PGRS proteins have coevolved with the antigenic ESX-V secretory system and are abundant in pathogenic Mycobacterium. Only a few PE_PGRS proteins have been characterized, and research suggests their role in organelle targeting, cell death pathways, calcium (Ca2+) homeostasis and disease pathogenesis. The PE_PGRS45 (Rv2615c) protein was predicted to contain mitochondria targeting sequences by in silico evaluation. Therefore, we investigated the targeting of the Rv2615c protein to host mitochondria and its effect on mitochondrial functions. In vitro experiments showed the Rv2615c protein colocalized with the mitochondria and led to morphological mitochondrial perturbations. Recombinant Rv2615c was observed to cause increased levels of intracellular reactive oxygen species and the adenosine diphosphate-to-adenosine triphosphate ratio. The Rv2615c protein also induced mitochondrial membrane depolarization and the generation of mitochondrial superoxide. We observed the release of cytochrome C into the cytoplasm and increased expression of proapoptotic genes Bax and Bim with no significant change in anti-apoptotic Bcl2 in Rv2615c-stimulated THP1 macrophages. Ca2+ is a key signaling molecule in tuberculosis pathogenesis, modulating host cell responses. As reported for other PE_PGRS proteins, Rv2615c also has Ca2+-binding motifs and thus can modulate calcium homeostasis in the host. We also observed a high level of Ca2+ influx in THP1 macrophages stimulated with Rv2615c. Based on these findings, we suggest that Rv2615c may be an effector protein that could contribute to disease pathogenesis by targeting host mitochondria.

PE_PGRS蛋白与抗原ESX-V分泌系统共进化,在致病分枝杆菌中含量丰富。只有少数PE_PGRS蛋白被表征,研究表明它们在细胞器靶向、细胞死亡途径、钙(Ca2+)稳态和疾病发病机制中的作用。通过计算机评估预测PE_PGRS45(Rv2615c)蛋白含有线粒体靶向序列。因此,我们研究了Rv2615c蛋白靶向宿主线粒体及其对线粒体功能的影响。体外实验表明,Rv2615c蛋白与线粒体共定位,并导致线粒体形态紊乱。观察到重组Rv22615c导致细胞内活性氧物质水平和二磷酸腺苷与三磷酸腺苷的比率增加。Rv2615c蛋白还诱导线粒体膜去极化和线粒体超氧化物的产生。我们观察到细胞色素C释放到细胞质中,并增加了促凋亡基因Bax和Bim的表达,而在Rv2615c刺激的THP1巨噬细胞中抗凋亡Bcl2没有显著变化。Ca2+是结核病发病机制中的一个关键信号分子,调节宿主细胞的反应。正如其他PE_PGRS蛋白所报道的那样,Rv2615c也具有Ca2+结合基序,因此可以调节宿主中的钙稳态。我们还观察到Rv2615c刺激的THP1巨噬细胞中有高水平的Ca2+内流。基于这些发现,我们认为Rv2615c可能是一种效应蛋白,通过靶向宿主线粒体参与疾病的发病机制。
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引用次数: 0
Singapore's diverse immunology landscape: interconnected research networks enabling blue sky ideas through to translation 新加坡多样化的免疫学格局:相互连接的研究网络使蓝天创意得以转化。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-07 DOI: 10.1111/imcb.12678
Jinmiao Chen, Nicholas Gascoigne, Jessica G Borger

Singapore stands as a dynamic hub for cutting-edge immunological research and innovation. The country's vibrant research ecosystem is supported by collaborative networks across the many national medical and scientific research institutes, fostering meaningful alliances between academia and industry. In this article, we speak to Assistant Professor Jinmiao Chen from the Agency for Science, Technology, and Research (A*STAR) and Professor Nicholas Gascoigne from the National University of Singapore (NUS), Duke-NUS Medical School and Nanyang Technological University (NTU) about immunology in Singapore. Credit: Kate Forbes.

新加坡是一个充满活力的尖端免疫学研究和创新中心。新加坡充满活力的科研生态系统得到了众多国家级医疗和科研机构合作网络的支持,促进了学术界与产业界之间有意义的联盟。在这篇文章中,我们采访了新加坡科技研究局(A*STAR)的陈金苗助理教授和新加坡国立大学(NUS)、杜克-新加坡国立大学医学院(Duke-NUS Medical School)和南洋理工大学(NTU)的尼古拉斯-加斯科因(Nicholas Gascoigne)教授,请他们谈谈新加坡的免疫学。图片来源:Kate Forbes。
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引用次数: 0
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Immunology & Cell Biology
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