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Peeking Into the Black Box of T Cell Receptor Signaling. 窥探T细胞受体信号传导的黑匣子。
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 Epub Date: 2024-06-14 DOI: 10.1146/annurev-immunol-090222-112028
Arthur Weiss

I have spent more than the last 40 years at the University of California, San Francisco (UCSF), studying T cell receptor (TCR) signaling. I was blessed with supportive mentors, an exceptionally talented group of trainees, and wonderful collaborators and colleagues during my journey who have enabled me to make significant contributions to our understanding of how the TCR initiates signaling. TCR signaling events contribute to T cell development as well as to mature T cell activation and differentiation.

在过去的40多年里,我一直在加州大学旧金山分校(UCSF)研究T细胞受体(TCR)信号传导。在我的旅程中,我有幸得到了支持我的导师、一群才华横溢的受训人员以及出色的合作者和同事,他们使我能够为我们理解TCR如何启动信号做出重大贡献。TCR信号传导事件有助于T细胞的发育以及成熟T细胞的活化和分化。《免疫学年度评论》第42卷预计最终在线出版日期为2024年4月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 0
Neuroimmunology of the Lung. 肺中的神经免疫相互作用。
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 Epub Date: 2024-06-14 DOI: 10.1146/annurev-immunol-083122-042512
Rossana Azzoni, Olaf Perdijk, Nicola L Harris, Benjamin J Marsland

Barrier tissues are highly innervated by sensory and autonomic nerves that are positioned in close proximity to both stromal and immune cell populations. Together with a growing awareness of the far-reaching consequences of neuroimmune interactions, recent studies have uncovered key mechanisms through which they contribute to organ homeostasis and immunity. It has also become clear that dysregulation of such interactions is implicated in the development of chronic lung diseases. This review describes the characteristics of the lung nervous system and discusses the molecular mechanisms that underlie lung neuroimmune interactions in infection and disease. We have contextualized the current literature and identified opportune areas for further investigation. Indeed, both the lung-brain axis and local neuroimmune interactions hold enormous potential for the exploration and development of novel therapeutic strategies targeting lung diseases.

屏障组织由感觉神经和自主神经高度支配,这些神经位于基质细胞和免疫细胞群附近。随着人们越来越意识到神经免疫相互作用的深远影响,最近的研究揭示了它们有助于器官稳态和免疫的关键机制。同样清楚的是,这种相互作用的失调与慢性肺部疾病的发展有关。本文综述了肺神经系统的特点,并讨论了感染和疾病中肺神经免疫相互作用的分子机制。我们对当前文献进行了背景分析,并确定了进一步调查的合适领域。事实上,肺脑轴和局部神经免疫相互作用对于探索和开发针对肺部疾病的新治疗策略具有巨大的潜力。预计免疫学年度评论第42卷的最终在线出版日期为2024年4月。修订后的估计数请参阅http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
Circadian Rhythms in Anticancer Immunity: Mechanisms and Treatment Opportunities. 抗癌免疫中的昼夜节律:机制与治疗机会。
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 DOI: 10.1146/annurev-immunol-090122-050842
Robert Pick, Chen Wang, Qun Zeng, Zeynep Melis Gül, Christoph Scheiermann

Circadian rhythms of approximately 24 h have emerged as important modulators of the immune system. These oscillations are important for mounting short-term, innate immune responses, but surprisingly also long-term, adaptive immune responses. Recent data indicate that they play a central role in antitumor immunity, in both mice and humans. In this review, we discuss the evolving literature on circadian antitumor immune responses and the underlying mechanisms that control them. We further provide an overview of circadian treatment regimens-chrono-immunotherapies-that harness time-of-day differences in immunity for optimal efficacy. Our aim is to provide an overview for researchers and clinicians alike, for a better understanding of the circadian immune system and how to best harness it for chronotherapeutic interventions. This knowledge is important for a better understanding of immune responses per se and could revolutionize the way we approach the treatment of cancer and a range of other diseases, ultimately improving clinical practice.

约 24 小时的昼夜节律已成为免疫系统的重要调节器。这些振荡对启动短期的先天性免疫反应很重要,但令人惊讶的是,对长期的适应性免疫反应也很重要。最近的数据表明,它们在小鼠和人类的抗肿瘤免疫中发挥着核心作用。在这篇综述中,我们将讨论有关昼夜节律抗肿瘤免疫反应及其潜在控制机制的不断发展的文献。我们进一步概述了昼夜节律治疗方案--同步免疫疗法--利用免疫的日时差异获得最佳疗效。我们的目的是为研究人员和临床医生提供一个概览,以便更好地了解昼夜节律免疫系统以及如何最好地利用它进行时间治疗干预。这些知识对于更好地了解免疫反应本身非常重要,并能彻底改变我们治疗癌症和其他一系列疾病的方法,最终改善临床实践。
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引用次数: 0
Immunology of Kidney Disease. 肾脏疾病免疫学。
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 Epub Date: 2024-06-14 DOI: 10.1146/annurev-immunol-090122-045843
Orestes Foresto-Neto, Luísa Menezes-Silva, Jefferson Antônio Leite, Magaiver Andrade-Silva, Niels Olsen Saraiva Câmara

The immune system and the kidneys are closely related. Immune components mediate acute kidney disease and are crucial to the progression of chronic kidney disease. Beyond its pathogenic functions, the immune system supports immunological homeostasis in healthy kidneys. The kidneys help maintain immune equilibrium by removing metabolic waste products and toxins, thereby limiting local and systemic inflammation. In this review, we describe the close relationship between the immune system and the kidneys. We discuss how the imbalance in the immune response can be deleterious to the kidneys and how immunomodulation can be important in preventing end-stage renal disease. In addition, recent tools such as in silico platforms and kidney organoids can help unveil the relationship between immune cells and kidney homeostasis.

免疫系统与肾脏密切相关。免疫成分介导急性肾脏疾病,对慢性肾脏疾病的进展至关重要。除了致病功能外,免疫系统还支持健康肾脏的免疫平衡。肾脏通过清除代谢废物和毒素来帮助维持免疫平衡,从而限制局部和全身炎症。在这篇综述中,我们将描述免疫系统与肾脏之间的密切关系。我们将讨论免疫反应失衡如何对肾脏造成损害,以及免疫调节如何在预防终末期肾病方面发挥重要作用。此外,硅学平台和肾脏有机体等最新工具有助于揭示免疫细胞与肾脏稳态之间的关系。免疫学年刊》(Annual Review of Immunology)第42卷的最终在线出版日期预计为2024年4月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
Microbial Metabolites and Gut Immunology. 微生物代谢物与肠道免疫学
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 DOI: 10.1146/annurev-immunol-090222-102035
Tadashi Takeuchi, Yumiko Nakanishi, Hiroshi Ohno

The intestine is the largest peripheral lymphoid organ in animals, including humans, and interacts with a vast array of microorganisms called the gut microbiota. Comprehending the symbiotic relationship between the gut microbiota and our immune system is essential not only for the field of immunology but also for understanding the pathogenesis of various systemic diseases, including cancer, cardiometabolic disorders, and extraintestinal autoimmune conditions. Whereas microbe-derived antigens are crucial for activating the intestinal immune system, particularly T and B cells, as environmental cues, microbes and their metabolites play a critical role in directing the differentiation of these immune cells. Microbial metabolites are regarded as messengers from the gut microbiota, since bacteria have the ability to produce unique molecules that humans cannot, and many immune cells in the intestine express receptors for these molecules. This review highlights the distinct relationships between microbial metabolites and the differentiation and function of the immune system.

肠道是包括人类在内的动物体内最大的外周淋巴器官,它与被称为肠道微生物群的大量微生物相互作用。理解肠道微生物群与我们免疫系统之间的共生关系不仅对免疫学领域至关重要,而且对理解各种全身性疾病(包括癌症、心脏代谢紊乱和肠道外自身免疫疾病)的发病机制也至关重要。微生物衍生的抗原作为环境线索对激活肠道免疫系统(尤其是 T 细胞和 B 细胞)至关重要,而微生物及其代谢物则在引导这些免疫细胞分化方面发挥着关键作用。微生物代谢物被视为来自肠道微生物群的信使,因为细菌有能力产生人类无法产生的独特分子,而肠道中的许多免疫细胞都表达这些分子的受体。本综述强调了微生物代谢物与免疫系统的分化和功能之间的独特关系。
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引用次数: 0
Ontogeny and Function of Plasmacytoid Dendritic Cells. 质体树突状细胞的本体和功能
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 DOI: 10.1146/annurev-immunol-090122-041105
Nicholas M Adams, Annesa Das, Tae Jin Yun, Boris Reizis

Plasmacytoid dendritic cells (pDCs) represent a unique cell type within the innate immune system. Their defining property is the recognition of pathogen-derived nucleic acids through endosomal Toll-like receptors and the ensuing production of type I interferon and other soluble mediators, which orchestrate innate and adaptive responses. We review several aspects of pDC biology that have recently come to the fore. We discuss emerging questions regarding the lineage affiliation and origin of pDCs and argue that these cells constitute an integral part of the dendritic cell lineage. We emphasize the specific function of pDCs as innate sentinels of virus infection, particularly their recognition of and distinct response to virus-infected cells. This essential evolutionary role of pDCs has been particularly important for the control of coronaviruses, as demonstrated by the recent COVID-19 pandemic. Finally, we highlight the key contribution of pDCs to systemic lupus erythematosus, in which therapeutic targeting of pDCs is currently underway.

类质体树突状细胞(pDCs)是先天性免疫系统中一种独特的细胞类型。它们的主要特性是通过内质体 Toll 样受体识别病原体衍生的核酸,并随之产生 I 型干扰素和其他可溶性介质,从而协调先天性和适应性反应。我们回顾了最近引人注目的 pDC 生物学的几个方面。我们讨论了有关 pDC 的系属和起源的新问题,并认为这些细胞构成了树突状细胞系的一个组成部分。我们强调了 pDCs 作为病毒感染先天哨兵的特殊功能,尤其是它们对病毒感染细胞的识别和独特反应。正如最近的 COVID-19 大流行所证明的那样,pDCs 的这种重要进化作用对于冠状病毒的控制尤为重要。最后,我们强调了 pDCs 对系统性红斑狼疮的关键贡献,目前针对 pDCs 的治疗正在进行中。
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引用次数: 0
B Cell-Directed Therapy in Autoimmunity. 自身免疫的B细胞定向治疗。
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 Epub Date: 2024-06-14 DOI: 10.1146/annurev-immunol-083122-044829
Ilana Abeles, Chris Palma, Nida Meednu, Aimee S Payne, R John Looney, Jennifer H Anolik

Autoimmune diseases with B cell-directed therapeutics approved by the US Food and Drug Administration are surprisingly diverse in clinical manifestations and pathophysiology. In this review, we focus on recent clinical and mechanistic insights into the efficacy of B cell depletion in these diverse autoimmune disorders, the rapidly expanding armamentarium of approved agents, and future approaches. The pathogenic roles for B cells include direct functions such as production of autoantibodies and proinflammatory cytokines and indirect functions via antigen presentation to T cells. The efficacy of B cell-depleting strategies varies across diseases and likely reflects the complexity of disease pathogenesis and relative contribution of B cell roles. Additionally, B cell-depleting therapies do not equally target all B cell subsets in all patients, and this likely explains some of the variability in responses. Recent reports of B cell depletion with novel chimeric antigen receptor (CAR) T cell approaches in an expanding number of autoimmune diseases highlight the potential role of B cell depletion in resetting immune tolerance. The relative importance of eliminating autoreactive B cells and plasma cells and approaches to doing so will also be discussed.

美国食品和药物管理局批准的B细胞导向治疗的自身免疫性疾病在临床表现和病理生理上惊人地多样化。在这篇综述中,我们将重点关注B细胞耗竭治疗这些不同自身免疫性疾病的临床和机制方面的最新见解,批准药物的迅速扩大,以及未来的方法。B细胞的致病作用包括直接功能,如产生自身抗体和促炎细胞因子,以及通过抗原向T细胞递呈的间接功能。B细胞消耗策略的功效因疾病而异,可能反映了疾病发病机制的复杂性和B细胞作用的相对贡献。此外,B细胞消耗疗法并不能平等地针对所有患者的所有B细胞亚群,这可能解释了反应的一些差异。最近有报道称,在越来越多的自身免疫性疾病中,使用新型嵌合抗原受体(CAR) T细胞方法去除B细胞,突出了B细胞去除在重设免疫耐受中的潜在作用。消除自身反应性B细胞和浆细胞的相对重要性以及这样做的方法也将被讨论。预计免疫学年度评论第42卷的最终在线出版日期为2024年4月。修订后的估计数请参阅http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
The Multifaceted Role of Tissue-Resident Memory T Cells. 组织驻留记忆 T 细胞的多重作用
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 DOI: 10.1146/annurev-immunol-101320-020220
Susan N Christo, Simone L Park, Scott N Mueller, Laura K Mackay

Regionalized immune surveillance relies on the concerted efforts of diverse memory T cell populations. Of these, tissue-resident memory T (TRM) cells are strategically positioned in barrier tissues, where they enable efficient frontline defense against infections and cancer. However, the long-term persistence of these cells has been implicated in a variety of immune-mediated pathologies. Consequently, modulating TRM cell populations represents an attractive strategy for novel vaccination and therapeutic interventions against tissue-based diseases. Here, we provide an updated overview of TRM cell heterogeneity and function across tissues and disease states. We discuss mechanisms of TRM cell-mediated immune protection and their potential contributions to autoimmune disorders. Finally, we examine how TRM cell responses might be durably boosted or dampened for therapeutic gain.

区域化免疫监视依赖于各种记忆 T 细胞群的协同努力。其中,组织驻留记忆 T 细胞(TRM)被战略性地安置在屏障组织中,在那里它们能对感染和癌症进行有效的前线防御。然而,这些细胞的长期存在与多种免疫介导的病症有关。因此,调节 TRM 细胞群是针对基于组织的疾病进行新型疫苗接种和治疗干预的一种有吸引力的策略。在此,我们将对TRM细胞在不同组织和疾病状态下的异质性和功能进行最新概述。我们讨论了 TRM 细胞介导的免疫保护机制及其对自身免疫性疾病的潜在贡献。最后,我们探讨了如何持久增强或抑制 TRM 细胞的反应以获得治疗效果。
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引用次数: 0
Priming and Maintenance of Adaptive Immunity in the Liver. 肝脏适应性免疫的启动和维持
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 Epub Date: 2024-06-14 DOI: 10.1146/annurev-immunol-090122-041354
Keigo Kawashima, Francesco Andreata, Cristian Gabriel Beccaria, Matteo Iannacone

The liver's unique characteristics have a profound impact on the priming and maintenance of adaptive immunity. This review delves into the cellular circuits that regulate adaptive immune responses in the liver, with a specific focus on hepatitis B virus infection as an illustrative example. A key aspect highlighted is the liver's specialized role in priming CD8+ T cells, leading to a distinct state of immune hyporesponsiveness. Additionally, the influence of the liver's hemodynamics and anatomical features, particularly during liver fibrosis and cirrhosis, on the differentiation and function of adaptive immune cells is discussed. While the primary emphasis is on CD8+ T cells, recent findings regarding the involvement of B cells and CD4+ T cells in hepatic immunity are also reviewed. Furthermore, we address the challenges ahead and propose integrating cutting-edge techniques, such as spatial biology, and combining mouse models with human sample analyses to gain comprehensive insights into the liver's adaptive immunity. This understanding could pave the way for novel therapeutic strategies targeting infectious diseases, malignancies, and inflammatory liver conditions like metabolic dysfunction-associated steatohepatitis and autoimmune hepatitis.

肝脏的独特特性对启动和维持适应性免疫有着深远的影响。本综述以乙型肝炎病毒感染为例,深入探讨调节肝脏适应性免疫反应的细胞回路。其中强调的一个关键方面是肝脏在启动 CD8+ T 细胞方面的特殊作用,这导致了一种独特的免疫低反应状态。此外,还讨论了肝脏血液动力学和解剖学特征对适应性免疫细胞分化和功能的影响,尤其是在肝纤维化和肝硬化期间。虽然主要重点是 CD8+ T 细胞,但也回顾了有关 B 细胞和 CD4+ T 细胞参与肝脏免疫的最新发现。此外,我们还探讨了未来的挑战,并建议整合空间生物学等尖端技术,将小鼠模型与人体样本分析相结合,以全面了解肝脏的适应性免疫。这种认识可为针对传染性疾病、恶性肿瘤以及非酒精性脂肪性肝炎和自身免疫性肝炎等炎症性肝病的新型治疗策略铺平道路。免疫学年评》第 42 卷的最终在线出版日期预计为 2024 年 4 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
Multilayered Immunity by Tissue-Resident Lymphocytes in Cancer. 癌症中组织驻留淋巴细胞的多层免疫作用
IF 26.9 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-06-01 Epub Date: 2024-06-14 DOI: 10.1146/annurev-immunol-083122-043836
Ming O Li, Jing Zhang, Zijian Xu, Xian Zhang, Peng Li, Andrew E Cornish

Lymphocytes spanning the entire innate-adaptive spectrum can stably reside in tissues and constitute an integral component of the local defense network against immunological challenges. In tight interactions with the epithelium and endothelium, tissue-resident lymphocytes sense antigens and alarmins elicited by infectious microbes and abiotic stresses at barrier sites and mount effector responses to restore tissue homeostasis. Of note, such a host cell-directed immune defense system has been recently demonstrated to surveil epithelial cell transformation and carcinoma development, as well as cancer cell metastasis at selected distant organs, and thus represents a primordial cancer immune defense module. Here we review how distinct lineages of tissue-resident innate lymphoid cells, innate-like T cells, and adaptive T cells participate in a form of multilayered cancer immunity in murine models and patients, and how their convergent effector programs may be targeted through both shared and private regulatory pathways for cancer immunotherapy.

跨越整个先天适应谱系的淋巴细胞可以稳定地驻留在组织中,并构成局部防御网络的一个组成部分,抵御免疫挑战。在与上皮细胞和内皮细胞的紧密互动中,组织驻留的淋巴细胞能感知屏障部位由传染性微生物和非生物压力引起的抗原和警报素,并启动效应反应以恢复组织的平衡。值得注意的是,这种由宿主细胞引导的免疫防御系统最近已被证实能监测上皮细胞转化和癌变发展,以及癌细胞在选定远处器官的转移,因此代表了一种原始的癌症免疫防御模块。在这里,我们回顾了组织驻留型先天性淋巴细胞、先天性类 T 细胞和适应性 T 细胞的不同品系是如何参与小鼠模型和患者的多层癌症免疫的,以及它们趋同的效应程序是如何通过共享和私有的调控途径成为癌症免疫疗法的靶点的。免疫学年刊》(Annual Review of Immunology)第 42 卷的最终在线出版日期预计为 2024 年 4 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
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引用次数: 0
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Annual review of immunology
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