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UNCovering new causes of monogenic systemic lupus erythematosus 联合国发现单基因系统性红斑狼疮的新病因。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-07-09 DOI: 10.1111/imcb.12807
Julia I Ellyard, Michael P Gantier

UNC93B1 is essential for the stability and endosomal trafficking of nucleic-acid sensing Toll-like receptors (TLRs) including TLR7 and TLR8. Increased TLR7 responses are associated with lupus autoimmunity in both mice and humans. In a recent article, Al-Azab et al. demonstrate the role of a variant of UNC93B1 (p.V117L) in the induction of pediatric systemic lupus erythematosus in patients and in mice through TLR7/8 hyperresponsiveness. They also highlight a potential role for the pharmacological inhibition of interleukin-1 receptor–associated kinase (IRAK) 1 and/or 4 in ameliorating disease.

UNC93B1 对于包括 TLR7 和 TLR8 在内的核酸感应 Toll 样受体 (TLR) 的稳定性和内体转运至关重要。TLR7 反应的增加与小鼠和人类的狼疮自身免疫有关。在最近的一篇文章中,Al-Azab 等人证明了 UNC93B1 的一个变体(p.V117L)在通过 TLR7/8 高反应性诱导患者和小鼠患上小儿系统性红斑狼疮中的作用。他们还强调了药物抑制白细胞介素-1 受体相关激酶 (IRAK) 1 和/或 4 在改善疾病方面的潜在作用。
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引用次数: 0
RAGging on recombination signal sequence strength for diffusion-mediated recombination 对扩散介导重组的重组信号序列强度进行 RAGging。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-07-07 DOI: 10.1111/imcb.12803
Katherine JL Jackson

In this article, we discuss new insights into the distinct mechanisms for V(D)J recombination for different immunoglobulin loci. This follows the recent revelation that recombination signal sequences (RSS) within the IGKV locus have evolved to be more efficient mediators of recombination activating gene (RAG) recombination compared to the same elements in the IGH locus. This difference in RSS strength is proposed to be driven by different molecular mechanisms for RAG-mediated recombination between the two loci.

在这篇文章中,我们讨论了不同免疫球蛋白基因座的 V(D)J 重组不同机制的新见解。这是继最近发现 IGKV 基因座中的重组信号序列(RSS)与 IGH 基因座中的相同元件相比,已进化为更有效的重组激活基因(RAG)重组介质之后的又一发现。这种 RSS 强度的差异被认为是由两个基因座之间 RAG 介导的重组的不同分子机制驱动的。
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引用次数: 0
Integrating functional metagenomics to decipher microbiome–immune interactions 整合功能元基因组学,破译微生物与免疫之间的相互作用。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-07-02 DOI: 10.1111/imcb.12798
Puspendu Sardar, Alexandre Almeida, Virginia A Pedicord

Microbial metabolites can be viewed as the cytokines of the microbiome, transmitting information about the microbial and metabolic environment of the gut to orchestrate and modulate local and systemic immune responses. Still, many immunology studies focus solely on the taxonomy and community structure of the gut microbiota rather than its functions. Early sequencing-based microbiota profiling approaches relied on PCR amplification of small regions of bacterial and fungal genomes to facilitate identification of the microbes present. However, recent microbiome analysis methods, particularly shotgun metagenomic sequencing, now enable culture-independent profiling of microbiome functions and metabolites in addition to taxonomic characterization. In this review, we showcase recent advances in functional metagenomics methods and applications and discuss the current limitations and potential avenues for future development. Importantly, we highlight a few examples of key areas of opportunity in immunology research where integrating functional metagenomic analyses of the microbiome can substantially enhance a mechanistic understanding of microbiome–immune interactions and their contributions to health and disease states.

微生物代谢产物可被视为微生物群的细胞因子,传递有关肠道微生物和代谢环境的信息,从而协调和调节局部和全身免疫反应。然而,许多免疫学研究只关注肠道微生物群的分类和群落结构,而不是其功能。早期以测序为基础的微生物群分析方法依赖于细菌和真菌基因组小区域的 PCR 扩增,以促进对存在的微生物的鉴定。然而,最近的微生物组分析方法,尤其是枪式元基因组测序法,现在除了分类学特征描述外,还能对微生物组的功能和代谢物进行不依赖培养的分析。在这篇综述中,我们展示了功能元基因组学方法和应用的最新进展,并讨论了目前的局限性和未来发展的潜在途径。重要的是,我们强调了免疫学研究中一些关键领域的例子,在这些领域中,整合微生物组的功能元基因组分析可大大提高对微生物组-免疫相互作用及其对健康和疾病状态的贡献的机理认识。
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引用次数: 0
Nurturing a positive research culture within your organization 在组织内部培养积极的科研文化。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-07-02 DOI: 10.1111/imcb.12804
Adrian Liston, Denise C Fitzgerald

Immunology & Cell Biology 2024; 102: 526; https://doi.org/10.1111/imcb.12804

Correction to: Immunology & Cell Biology 2023; https://doi.org/10.1111/imcb.12795

The authors would like to correct the descriptions for Figures 2 and 3. Please refer to the correct captions as shown below.

Immunology & Cell Biology 2024; 102: 526; https://doi.org/10.1111/imcb.12804Correction to:Immunology & Cell Biology 2023; https://doi.org/10.1111/imcb.12795The 作者希望更正图 2 和图 3 的描述。请参考以下所示的正确标题。
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引用次数: 0
Highlight of 2023: Advances in germinal centers 2023 年的亮点:生殖中心的进步
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-06-30 DOI: 10.1111/imcb.12800
Theresa E Pankhurst, Michelle A Linterman

In this article for the Highlight of 2023 series, we discuss recent advances in the fundamental biology of the germinal center response. These discoveries provide important insights as to how the germinal center contributes to protection against infection, and also highlights opportunities for future vaccine development.

在这篇 "2023 年亮点 "系列文章中,我们将讨论生殖中心反应基础生物学的最新进展。这些发现提供了关于生殖中心如何有助于抵御感染的重要见解,同时也凸显了未来疫苗开发的机遇。
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引用次数: 0
From dentistry to immunology: navigating challenges and building a career in neuroimmunology. 从牙科到免疫学:迎接挑战,开创神经免疫学事业。
IF 3.2 4区 医学 Q1 Medicine Pub Date : 2024-06-27 DOI: 10.1111/imcb.12797
Lidia Yshii

This Commentary recounts an academic journey from dentistry to neuroimmunology, highlighting pivotal moments such as a PhD fraught with challenges and an unexpected postdoctoral experience in France. My decision to settle in Belgium for a postdoc and subsequent transition to an assistant professorship at KU Leuven reflects resilience, adaptability and a commitment to both scientific exploration and family life. Balancing career uncertainties, motherhood and academic achievements, it encapsulates a trajectory shaped by a passion for neuroimmunology.

这篇评论记述了我从牙科到神经免疫学的学术历程,突出了一些关键时刻,如充满挑战的博士生涯和在法国意外的博士后经历。我决定到比利时做博士后,随后又转到鲁汶大学担任助理教授,这反映了我的韧性、适应能力以及对科学探索和家庭生活的承诺。在职业生涯的不确定性、母亲身份和学术成就之间取得平衡,体现了我对神经免疫学的热情所塑造的人生轨迹。
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引用次数: 0
Striking an alliance between T cells and macrophages for enhanced cancer immunotherapy 在 T 细胞和巨噬细胞之间建立联盟,增强癌症免疫疗法。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-06-27 DOI: 10.1111/imcb.12799
Tessa Gargett, Lisa M Ebert

A new study by Yamada-Hunter et al. reveals a novel approach to promote synergy—rather than antagonism—between macrophages and engineered T cells, leading to enhanced antitumor immunity.

Yamada-Hunter 等人的一项新研究揭示了一种促进巨噬细胞与工程 T 细胞之间协同作用而非拮抗作用的新方法,从而增强了抗肿瘤免疫力。
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引用次数: 0
Helminth infection induces a distinct subset of CD101hi lung tissue–infiltrating eosinophils that are differentially regulated by type 2 cytokines 螺旋体感染会诱导不同的 CD101hi 肺组织浸润性嗜酸性粒细胞亚群,这些亚群受 2 型细胞因子的不同调节。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-06-26 DOI: 10.1111/imcb.12796
Sophia-Louise Noble, Francesco Vacca, Kerry L Hilligan, Thomas C Mules, Graham Le Gros, Stephen Inns

Eosinophils play divergent roles in health and disease, contributing to both immunoregulatory and proinflammatory responses. Helminth infection is strongly associated with eosinophilia and the induction of the type 2 cytokines interleukin (IL)-5, IL-4 and IL-13. This study aimed to elucidate the heterogeneity of pulmonary eosinophils in response to helminth infection and the roles of IL-5, IL-4 and IL-13 in driving pulmonary eosinophil responses. Using the murine helminth model Nippostrongylus brasiliensis (Nb), we characterize a subtype of eosinophils, defined by high expression of CD101, that is induced in the lungs of Nb-infected mice and are phenotypically distinct from lung eosinophils that express low levels of CD101. Strikingly, we show that the two eosinophil subtypes have distinct anatomical localization within the lung: CD101low eosinophils are predominantly localized in the lung vasculature, whereas Nb-induced CD101hi eosinophils are predominantly localized in the extravascular lung niche. We show that CD101hi eosinophils are also induced across other models of pulmonary infection and inflammation, including a nonlung-migrating helminth infection, house dust mite–induced allergic inflammation and influenza infection. Furthermore, we demonstrate that the induction of CD101hi tissue eosinophils is independent of IL-5 and IL-4 signaling, but is dependent on intact IL-13 signaling. These results suggest that IL-13 produced during helminth infection and other disease states promotes a pulmonary tissue-infiltrating program in eosinophils defined by high expression of CD101.

嗜酸性粒细胞在健康和疾病中发挥着不同的作用,既能促进免疫调节,也能促进炎症反应。蠕虫感染与嗜酸性粒细胞增多以及诱导白细胞介素(IL)-5、IL-4 和 IL-13 等 2 型细胞因子密切相关。本研究旨在阐明肺嗜酸性粒细胞对蠕虫感染反应的异质性,以及IL-5、IL-4和IL-13在驱动肺嗜酸性粒细胞反应中的作用。通过使用小鼠蠕虫模型巴西嗜酸性粒细胞绦虫(Nb),我们确定了嗜酸性粒细胞亚型的特征,该亚型由 CD101 的高表达所定义,可在 Nb 感染小鼠的肺部诱导,在表型上有别于低表达 CD101 的肺嗜酸性粒细胞。引人注目的是,我们发现这两种嗜酸性粒细胞亚型在肺内有不同的解剖定位:CD101low 嗜酸性粒细胞主要定位于肺血管,而 Nb 诱导的 CD101hi 嗜酸性粒细胞则主要定位于血管外肺龛。我们的研究表明,CD101hi 嗜酸性粒细胞在其他肺部感染和炎症模型中也能被诱导,包括非肺部移行蠕虫感染、屋尘螨诱导的过敏性炎症和流感感染。此外,我们还证明 CD101hi 组织嗜酸性粒细胞的诱导与 IL-5 和 IL-4 信号传导无关,但依赖于完整的 IL-13 信号传导。这些结果表明,在蠕虫感染和其他疾病状态下产生的 IL-13 促进了嗜酸性粒细胞的肺组织浸润程序,该程序由 CD101 的高表达所定义。
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引用次数: 0
The immune checkpoint TIGIT is upregulated on T cells during bacterial infection and is a potential target for immunotherapy 在细菌感染过程中,免疫检查点 TIGIT 在 T 细胞中上调,是免疫疗法的潜在靶点。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-06-14 DOI: 10.1111/imcb.12794
Timothy R McCulloch, Gustavo R Rossi, Socorro Miranda-Hernandez, Ana Maria Valencia-Hernandez, Louisa Alim, Clemence J Belle, Andrew Krause, Lucia F Zacchi, Pui Yeng Lam, Kyohei Nakamura, Andreas Kupz, Timothy J Wells, Fernando Souza-Fonseca-Guimaraes

Antibiotic resistance is a major public health threat, and alternatives to antibiotic therapy are urgently needed. Immunotherapy, particularly the blockade of inhibitory immune checkpoints, is a leading treatment option in cancer and autoimmunity. In this study, we used a murine model of Salmonella Typhimurium infection to investigate whether immune checkpoint blockade could be applied to bacterial infection. We found that the immune checkpoint T-cell immunoglobulin and ITIM domain (TIGIT) was significantly upregulated on lymphocytes during infection, particularly on CD4+ T cells, drastically limiting their proinflammatory function. Blockade of TIGIT in vivo using monoclonal antibodies was able to enhance immunity and improve bacterial clearance. The efficacy of anti-TIGIT was dependent on the capacity of the antibody to bind to Fc (fragment crystallizable) receptors, giving important insights into the mechanism of anti-TIGIT therapy. This research suggests that targeting immune checkpoints, such as TIGIT, has the potential to enhance immune responses toward bacteria and restore antibacterial treatment options in the face of antibiotic resistance.

抗生素耐药性是一个重大的公共卫生威胁,因此迫切需要抗生素疗法的替代品。免疫疗法,尤其是阻断抑制性免疫检查点,是癌症和自身免疫的主要治疗选择。在这项研究中,我们使用鼠伤寒沙门氏菌感染模型来研究免疫检查点阻断是否可用于细菌感染。我们发现,在感染过程中,免疫检查点T细胞免疫球蛋白和ITIM结构域(TIGIT)在淋巴细胞上显著上调,尤其是在CD4+ T细胞上,极大地限制了它们的促炎功能。在体内使用单克隆抗体阻断 TIGIT 能够增强免疫力,提高细菌清除率。抗TIGIT的疗效取决于抗体与Fc(可结晶片段)受体结合的能力,这为了解抗TIGIT疗法的机制提供了重要依据。这项研究表明,靶向免疫检查点(如 TIGIT)有可能增强对细菌的免疫反应,并在抗生素耐药性面前恢复抗菌治疗选择。
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引用次数: 0
Transcriptional network analysis of peripheral blood leukocyte subsets in multiple sclerosis identifies a pathogenic role for a cytotoxicity-associated gene network in myeloid cells 多发性硬化症外周血白细胞亚群的转录网络分析确定了骨髓细胞中细胞毒性相关基因网络的致病作用。
IF 3.2 4区 医学 Q3 CELL BIOLOGY Pub Date : 2024-06-14 DOI: 10.1111/imcb.12793
Margaret A Jordan, Melissa M Gresle, Adrian T Gemiarto, Dragana Stanley, Letitia D Smith, Louise Laverick, Tim Spelman, Jim Stankovich, Annie ML Willson, Xuyen T Dinh, Laura Johnson, Kylie Robertson, Christopher AR Reid, Judith Field, Helmut Butzkueven, Alan G Baxter

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system affecting predominantly adults. It is a complex disease associated with both environmental and genetic risk factors. Although over 230 risk single-nucleotide polymorphisms have been associated with MS, all are common human variants. The mechanisms by which they increase the risk of MS, however, remain elusive. We hypothesized that a complex genetic phenotype such as MS could be driven by coordinated expression of genes controlled by transcriptional regulatory networks. We, therefore, constructed a gene coexpression network from microarray expression analyses of five purified peripheral blood leukocyte subsets of 76 patients with relapsing remitting MS and 104 healthy controls. These analyses identified a major network (or module) of expressed genes associated with MS that play key roles in cell-mediated cytotoxicity which was downregulated in monocytes of patients with MS. Manipulation of the module gene expression was achieved in vitro through small interfering RNA gene knockdown of identified drivers. In a mouse model, network gene knockdown modulated the autoimmune inflammatory MS model disease—experimental autoimmune encephalomyelitis. This research implicates a cytotoxicity-associated gene network in myeloid cells in the pathogenesis of MS.

多发性硬化症(MS)是一种主要影响成年人的中枢神经系统自身免疫性疾病。这是一种与环境和遗传风险因素相关的复杂疾病。尽管有 230 多种风险单核苷酸多态性与多发性硬化症有关,但它们都是常见的人类变异。然而,它们增加多发性硬化症风险的机制仍然难以捉摸。我们假设,多发性硬化症等复杂的遗传表型可能是由转录调控网络控制的基因协调表达驱动的。因此,我们通过对 76 名复发缓解型多发性硬化症患者和 104 名健康对照者的五个纯化外周血白细胞亚群进行芯片表达分析,构建了一个基因共表达网络。这些分析确定了一个与多发性硬化症相关的主要表达基因网络(或模块),这些基因在细胞介导的细胞毒性中发挥关键作用,而多发性硬化症患者的单核细胞中这些基因表达下调。通过小干扰 RNA 基因敲除确定的驱动基因,在体外实现了对模块基因表达的控制。在小鼠模型中,网络基因敲除调节了自身免疫炎症性多发性硬化症模型疾病--实验性自身免疫性脑脊髓炎。这项研究表明,髓系细胞中的细胞毒性相关基因网络与多发性硬化症的发病机制有关。
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引用次数: 0
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Immunology & Cell Biology
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