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Uncoupling of Natural Killer cell functional maturation and cytolytic function in NOD mice NOD小鼠自然杀伤细胞功能成熟和细胞溶解功能的解耦
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-03 DOI: 10.1111/imcb.12676
Capucine Bourel, Victor Mullins-Dansereau, Maher Al Khaldi, Geneviève Chabot-Roy, Félix Lombard-Vadnais, Sylvie Lesage

NK cells are innate immune cells that target infected and tumor cells. Mature NK (mNK) cells undergo functional maturation characterized by four distinct stages, during which they acquire their cytotoxic properties. mNK cells from non-obese diabetic (NOD) mice exhibit a defect in functional maturation and have impaired cytotoxic functions. Hence, we tested whether the impaired cytotoxic function observed in mNK cells from NOD mice can be explained by their defect in functional maturation. By comparing the function of mNK cells from B6, B6g7 and NOD mice, we show that the expression of granzyme B is severely impaired in mNK cells from NOD mice, agreeing with their inability to control tumor growth in vivo. The low level of granzyme B expression in mNK cells from NOD mice is found at all stages of functional maturation and is therefore independent of their functional maturation defect. Consequently, this study demonstrates that phenotypic functional maturation of mNK cells can be uncoupled from the acquisition of cytotoxic functions.

NK细胞是针对感染细胞和肿瘤细胞的先天免疫细胞。成熟的NK(mNK)细胞经历以四个不同阶段为特征的功能成熟,在这四个阶段中,它们获得了细胞毒性特性。来自非肥胖糖尿病(NOD)小鼠的mNK细胞表现出功能成熟缺陷并且具有受损的细胞毒性功能。因此,我们测试了在NOD小鼠的mNK细胞中观察到的细胞毒性功能受损是否可以用其功能成熟缺陷来解释。通过比较B6、B6g7和NOD小鼠的mNK细胞的功能,我们发现颗粒酶B在NOD小鼠mNK细胞中的表达严重受损,这与它们在体内无法控制肿瘤生长一致。来自NOD小鼠的mNK细胞中颗粒酶B的低水平表达在功能成熟的所有阶段都被发现,因此与它们的功能成熟缺陷无关。因此,本研究表明,mNK细胞的表型功能成熟可以与细胞毒性功能的获得脱钩。
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引用次数: 0
Reimagining possibilities: the journey of a PhD parent 重新想象各种可能性:一位博士家长的心路历程。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-08-01 DOI: 10.1111/imcb.12671
Kim Maree O'Sullivan

In this commentary, I discuss my non-traditional pathway to a PhD, a late-bloomer's account of balancing a young family and PhD studies, a guide for those contemplating the same path.

在这篇评论中,我讨论了自己非传统的博士之路,一个大器晚成的人如何在年轻家庭和博士学习之间取得平衡,为正在考虑走同样道路的人提供指导。
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引用次数: 0
The immunology ecosystem in South Africa: striking an equitable balance between fostering discovery, promoting translation and capacity building 南非的免疫学生态系统:在促进发现、推动转化和能力建设之间实现公平平衡。
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-07-31 DOI: 10.1111/imcb.12672
Clive M Gray, Jessica G Borger

In the vast and diverse continent of Africa, the field of immunology holds immense significance as it navigates the complex landscape of infectious diseases and public health challenges. In this article, we speak with Professor Clive Gray, who provides powerful and valuable insights into the unique research opportunities and immunological advancements supported by Africa's unique blend of social, economic and environmental factors and also discusses the societal and cultural challenges that need to be overcome for equitable research to be achieved across the continent.

在广袤而多样的非洲大陆,免疫学领域在应对传染病和公共卫生挑战的复杂局面中发挥着巨大的作用。在这篇文章中,我们采访了克莱夫-格雷(Clive Gray)教授,他就非洲独特的社会、经济和环境因素所带来的独特研究机会和免疫学进步提供了有力而有价值的见解,并讨论了在非洲大陆实现公平研究需要克服的社会和文化挑战。
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引用次数: 0
Activators of neurotoxic microglia in neurodegeneration: is the answer in blood? 神经变性过程中的神经毒性小胶质细胞活化剂:答案在血液中吗?
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-07-31 DOI: 10.1111/imcb.12674
Caitlin A Finney, Heather M Wilkins, Russell H Swerdlow, David A Brown

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引用次数: 0
Mapping the two distinct proliferative bursts early in T-cell development 绘制t细胞发育早期的两种不同的增殖爆发
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-07-19 DOI: 10.1111/imcb.12670
Seungyoul Oh, Dhruti Parikh, Jiyao Xiao, Xin Liu, Karen Gu, Mark MW Chong

T-cell development occurs in the thymus and is tightly regulated to produce a diverse enough repertoire of mature T cells that can recognize any potential pathogen. The development of T cells is dependent on small numbers of uncommitted precursors that continually seed the thymus from the bone marrow. As they progress along the developmental pathway, there is a massive expansion in cell number to generate the necessary diversity in T-cell receptor chain usage. It is recognized that there are two proliferative bursts that occur early in T-cell development, one prior to β-selection and one after, and these are responsible for the expansion. While the proliferation following β-selection is well-characterized, the earlier proliferative burst has yet to be precisely defined. In this study, we employ single-cell RNA sequencing coupled to trajectory inference methods to pinpoint when in T-cell development thymocytes are induced into cell cycle. We show that the first proliferative burst is initiated in the double-negative (DN) 2a stage before T lineage commitment occurs, with cell cycling downregulated by the DN3a stage. A second burst is then initiated at the DN3b stage, immediately after β-selection. We subsequently employ fluorescence-activated cell sorting–based analysis for DNA content to confirm these two proliferative bursts.

T细胞的发育发生在胸腺中,并受到严格的调控,以产生足够多样化的成熟T细胞,这些成熟T细胞可以识别任何潜在的病原体。T细胞的发育依赖于少量未确定的前体,这些前体不断地从骨髓中植入胸腺。随着它们在发育途径上的进展,细胞数量大量增加,以产生t细胞受体链使用的必要多样性。人们认识到,在t细胞发育早期有两次增殖爆发,一次发生在β选择之前,一次发生在β选择之后,它们负责扩增。虽然β选择后的增殖已被很好地描述,但早期的增殖爆发尚未被精确定义。在这项研究中,我们采用单细胞RNA测序结合轨迹推断方法来确定t细胞发育过程中胸腺细胞何时被诱导进入细胞周期。我们发现,在T谱系发生之前,第一次增殖爆发是在双阴性(DN) 2a阶段开始的,细胞周期在DN3a阶段下调。在β选择后,DN3b阶段立即开始第二次爆发。我们随后采用荧光激活细胞分选为基础的DNA含量分析,以确认这两个增殖爆发。
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引用次数: 0
Strategic career building during your PhD: a timeline for maximizing your opportunities 博士期间的战略职业建设:最大限度地利用机会的时间表
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-07-12 DOI: 10.1111/imcb.12668
Adrian Liston, Lydia E Makaroff

PhD training can be incredibly versatile, leading to many downstream careers. There is potential to gain training to help you enter any of these careers after graduation. However, it is often only in retrospect that the options and optimal strategies become clear. Here we provide a strategic framework to empower PhD researchers to build and expand their career options in a method compatible with tomorrow's career ecosystem. The strategic framework encourages early career researchers to take a self-directed approach to establish flexible career goals, diversify exposures and build professional networks. Researchers increase their chances of success by building early markers of multiple career pathways into their PhD program. The framework emphasizes self-direction, adaptability and resilience, enabling early career researchers to embrace new opportunities and to navigate uncertainties. This structured approach empowers PhD researchers to maximize their opportunities, positioning them for long-term success in the various career options within and beyond academia.

博士培训可以是令人难以置信的多才多艺,导致许多下游的职业生涯。有可能获得培训,帮助你在毕业后进入这些职业。然而,往往只有在回顾过去时,选择和最佳战略才变得清晰。在这里,我们提供了一个战略框架,使博士研究人员能够以与未来职业生态系统兼容的方法建立和扩大他们的职业选择。该战略框架鼓励早期职业研究人员采取自我导向的方法,建立灵活的职业目标,使接触多样化,并建立专业网络。研究人员通过在他们的博士项目中建立多种职业道路的早期标志来增加他们成功的机会。该框架强调自我指导、适应性和韧性,使早期职业研究人员能够接受新的机会并应对不确定性。这种结构化的方法使博士研究人员能够最大限度地利用他们的机会,使他们在学术界内外的各种职业选择中取得长期成功。
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引用次数: 0
SARS-CoV-2 clearance after breakthrough infection correlates with fit and happy cells 突破感染后SARS-CoV-2清除与健康和快乐细胞相关
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-07-04 DOI: 10.1111/imcb.12667
Marc Veldhoen, Antonio Bertoletti

Immunology & Cell Biology 2023; 101: 672; https://doi.org/10.1111/imcb.12667

Correction to: Immunology & Cell Biology 2023; https://doi.org/10.1111/imcb.12654

Conflicts of Interest were omitted from this article. This information appears below. The authors apologize for this error.

A Bertoletti reports a pending patent for a method to monitor SARS-CoV-2-specific T cells in biological samples. He is also co-founder and owns shares in (a) LION TCR, a biotech company developing T cell therapy against virus-related cancers, and (b) T-cell Diagnostic, a company providing immunological monitoring in clinical samples.

免疫学,细胞生物学2023;101: 672;https://doi.org/10.1111/imcb.12667Correction到:免疫学&细胞生物学2023;https://doi.org/10.1111/imcb.12654Conflicts of Interest在本文中被省略。该信息如下所示。作者为这个错误道歉。Bertoletti报告了一项正在申请中的专利,该专利用于监测生物样本中sars - cov -2特异性T细胞的方法。他也是(a) LION TCR(开发针对病毒相关癌症的T细胞疗法的生物技术公司)和(b) T细胞诊断(提供临床样本免疫监测的公司)的联合创始人并拥有股份。
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引用次数: 0
You Wnt some, you lose none: lessons learnt from a non-canonical immunology educator 你想要一些,你就不会失去:从一个非正统免疫学教育家那里学到的教训
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-07-02 DOI: 10.1111/imcb.12663
Samy Sakkal

Pathways to tenured teaching positions are fraught with obstacles and require a combination of luck, perseverance and a competitive track record. Despite this, there are strategies that one can employ to increase your chances of success but, first and foremost, one must be an excellent communicator. Excellent communicators make for talented teachers, but one must also enjoy teaching or risk energy, i.e. your students will lack (co)stimulation. Academics who are new to teaching immunology need support from their community of practise (such as ASI Education Special Interest Groups) given that immunology can be challenging to teach. For every rule that we teach our students, there are equally many exceptions that confuse and confound. The complexity of our discipline also owes to the highly conceptual curriculum and abstract discipline language. To this end, this work seeks to provide advice to current and aspiring early-career immunology educators, utilising lessons learnt from my experience as an academic over the last decade. Topics include: understanding the needs of the student cohort; active learning strategies to engage students; ethical dilemmas for publishing pedagogical papers and the attainability of tenure. Like exogenously processed antigens, there is no hard and fast rule about one's pathway to academia; some take the canonical road (MHC class II) and others break the rules (cross-presentation). Whichever the path, teaching is a rewarding career and as long as you view your students as collaborators you have nothing to lose.

通往终身教职的道路充满了障碍,需要运气、毅力和竞争记录的结合。尽管如此,还是有一些策略可以用来增加你成功的机会,但首先,你必须是一个优秀的沟通者。优秀的沟通者造就了才华横溢的教师,但一个人也必须享受教学或冒险能量,即你的学生将缺乏(co)激励。刚开始教授免疫学的学者需要他们的实践社区(如ASI教育特殊兴趣小组)的支持,因为免疫学的教学可能具有挑战性。对于我们教给学生的每一条规则,都有同样多的令人困惑和困惑的例外。我们学科的复杂性也与高度概念化的课程和抽象的学科语言有关。为此,这项工作旨在为当前和有抱负的早期职业免疫学教育者提供建议,利用我过去十年作为学者的经验教训。主题包括:了解学生群体的需求;主动学习策略吸引学生参与;出版教学论文的伦理困境与终身教职的可得性。就像外源性加工抗原一样,通往学术界的道路没有硬性规定;一些人走规范路线(MHC II类),另一些人则打破规则(交叉呈现)。无论走哪条路,教学都是一项有回报的职业,只要你把学生视为合作者,你就没有什么可失去的。
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引用次数: 0
Help is on the way: critical roles of CD4+ T cells in infection and vaccination 帮助就在路上:CD4+ T细胞在感染和疫苗接种中的关键作用
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-07-01 DOI: 10.1111/imcb.12662
Laura Cook, C. Mee Ling Munier

The July 2023 issue contains a Special Feature about CD4+ T cells in infection and vaccination. CD4+ T helper cells are composed of many specialized subsets that play critical roles in immune memory. These cells have been somewhat overshadowed in the infectious disease and vaccination literature by their CD8+ counterparts and B cells/antibodies, which have been easier to study with available techniques. Therefore, we designed this issue to shine a light on some of the latest knowledge on how CD4+ T cells contribute to protective immunity. This Special Feature includes both original research and review articles on techniques to study CD4+ T-cell subsets and their roles in influenza A virus or human papilloma virus infection, sepsis and following vaccination to severe acute respiratory syndrome coronavirus 2. This collection highlights how new techniques are enabling rapid knowledge gain on how these cells underpin key aspects of the generation of effective immune responses, information that will be essential for the treatment and prevention of infectious diseases.

《2023年7月刊》载有关于CD4+ T细胞感染和疫苗接种的专题。CD4+ T辅助细胞由许多在免疫记忆中起关键作用的特殊亚群组成。在传染病和疫苗文献中,这些细胞在某种程度上被它们的CD8+对应物和B细胞/抗体所掩盖,B细胞/抗体更容易用现有技术进行研究。因此,我们设计了这一期来揭示一些关于CD4+ T细胞如何促进保护性免疫的最新知识。本专题包括研究CD4+ t细胞亚群及其在甲型流感病毒或人乳头瘤病毒感染、败血症和接种严重急性呼吸综合征冠状病毒疫苗2中的作用的技术的原始研究和评论文章。这一集合强调了新技术如何使人们能够快速获得关于这些细胞如何支持产生有效免疫反应的关键方面的知识,这些信息对治疗和预防传染病至关重要。
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引用次数: 0
A guide to relocating your laboratory 实验室搬迁指南
IF 4 4区 医学 Q3 CELL BIOLOGY Pub Date : 2023-06-27 DOI: 10.1111/imcb.12665
Adrian Liston, James Dooley

Research positions have become increasingly less stable, thus increasing the frequency at which research laboratories need to be relocated. A laboratory relocation can be a positive transition for you and your team; however, it requires careful planning in order to minimize the disruption and mitigate potential harms. Here we discuss key planning steps involved in successfully relocating your laboratory.

研究职位变得越来越不稳定,从而增加了研究实验室需要搬迁的频率。实验室搬迁对您和您的团队来说是一个积极的转变;然而,它需要仔细的规划,以尽量减少干扰和减轻潜在的危害。在这里,我们讨论成功搬迁实验室所涉及的关键规划步骤。
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引用次数: 0
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Immunology & Cell Biology
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