Immunity最新文献

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Innate type 2 lymphocytes trigger an inflammatory switch in alveolar macrophages 先天2型淋巴细胞触发肺泡巨噬细胞的炎症开关

IF 32.4 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-11 DOI: 10.1016/j.immuni.2025.11.015

Stijn Verwaerde, Jean-François Hastir, Sjoerd T.T. Schetters, Ursula Smole, Leen Seys, Antonio P. Baptista, Kieran English, Martijn J. Schuijs, Helena Aegerter, Karel F.A. Van Damme, Aimée Bugler-Lamb, Nikita Gerebtsov, Wendy Toussaint, Tatsuma Ban, Tomohiko Tamura, Florent Ginhoux, Zhaoyuan Liu, Wouter Saelens, Hamida Hammad, Martin Guilliams, Bart N. Lambrecht

引用次数: 0

Tolerance to ferroptosis facilitates lipid metabolism and pathogenic type 2 immunity in allergic airway inflammation 对铁下垂的耐受促进了过敏性气道炎症中的脂质代谢和致病性2型免疫

IF 32.4 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-10 DOI: 10.1016/j.immuni.2025.11.018

Chantal Wientjens, Maria Doverman, Jelena Zurkovic, Tushar More, Jayagopi Surendar, Svetozar Nesic, Carola Sarici, Timon D. Utecht, Johanna Pohl, Jonathan Pollock, David Voehringer, Karsten Hiller, Christoph Thiele, Christoph Wilhelm

Type 2 innate lymphoid cells (ILC2s) are essential for maintaining and protecting barrier tissues, but they also drive chronic inflammation, a process associated with altered metabolic activity. Identifying and targeting the metabolic pathways driving ILC2-mediated inflammation could restore tissue homeostasis. Here, we find that in allergic airway inflammation, pathogenic ILC2s rely on cystine for enhanced metabolic flexibility and survival. Cystine acquisition fuels glutathione (GSH) synthesis, which, together with increased expression of glutathione peroxidase 4 (GPX4) and thioredoxin reductase 1 (TXNRD1), confers resistance to ferroptosis by counteracting lipid peroxidation and reactive oxygen species (ROS). This adaptation enables accelerated lipid acquisition and metabolism, fostering ILC2 and T helper type 2 (Th2) cell expansion. Conversely, ablation of GPX4 and TXNRD1 in ILC2s or pharmacological inhibition of TXNRD1 constrains lipid metabolism and prevents ILC2 accumulation in allergen-induced airway inflammation. This demonstrates that increased reliance on antioxidant systems represents a metabolic vulnerability that can be exploited therapeutically to treat asthma.

2型先天淋巴样细胞（ILC2s）对于维持和保护屏障组织至关重要，但它们也会引发慢性炎症，这一过程与代谢活动的改变有关。识别和靶向驱动ilc2介导的炎症的代谢途径可以恢复组织稳态。本研究发现，在变应性气道炎症中，致病性ILC2s依赖胱氨酸增强代谢灵活性和生存。胱氨酸获取促进谷胱甘肽（GSH）的合成，与谷胱甘肽过氧化物酶4 （GPX4）和硫氧还蛋白还原酶1 （TXNRD1）的表达增加一起，通过对抗脂质过氧化和活性氧（ROS），赋予铁死亡抗性。这种适应能够加速脂质获取和代谢，促进ILC2和T辅助型2 （Th2）细胞的扩增。相反，消融ILC2s中的GPX4和TXNRD1或药理抑制TXNRD1可抑制脂质代谢并阻止ILC2在过敏原诱导的气道炎症中的积累。这表明，对抗氧化系统的依赖增加代表了一种代谢脆弱性，可以用于治疗哮喘。

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引用次数: 0

A surprising link: TET2 clonal hematopoiesis boosts immune checkpoint therapy 一个令人惊讶的联系：TET2克隆造血促进免疫检查点治疗

IF 32.4 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-09 DOI: 10.1016/j.immuni.2025.11.012

Qiang Dong, Chengcheng Jin

TET2 mutations can drive clonal hematopoiesis (CH), but their impact on tumor immunity remains unresolved. Recently in Cancer Cell, Herbrich et al. reported that TET2-mutant CH reprograms tumor-associated macrophages to enhance antigen presentation and immune-checkpoint therapy efficacy in solid tumors.

TET2突变可以驱动克隆造血（CH），但其对肿瘤免疫的影响尚不清楚。最近在Cancer Cell杂志上，Herbrich等人报道tet2突变CH重编程肿瘤相关巨噬细胞，以增强实体肿瘤的抗原呈递和免疫检查点治疗效果。

引用次数: 0

Memories are I(F)N-credibly protective 记忆是I(F) n可信的保护

IF 32.4 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-09 DOI: 10.1016/j.immuni.2025.11.016

Brydie R. Huckestein, Paul G. Thomas

Lung-resident memory CD8⁺ T cells coordinate rapid antiviral defense mechanisms across lung compartments to quicky limit viral replication and spread. In this issue of Immunity, Mattingly et al. demonstrate the importance of CD8⁺ Trm cell-derived interferon-γ in epithelial reprogramming for barrier defense in humans.

肺驻留记忆CD8+ T细胞协调跨肺室的快速抗病毒防御机制，以快速限制病毒复制和传播。在这一期的《免疫》杂志上，Mattingly等人证明了CD8+ Trm细胞来源的干扰素-γ在人类上皮重编程屏障防御中的重要性。

引用次数: 0

The history and promise of Treg cells Treg细胞的历史和前景

IF 32.4 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-09 DOI: 10.1016/j.immuni.2025.11.011

Christophe Benoist, Dario A.A. Vignali, Richard A. Flavell, Diane Mathis

The seminal discoveries that established the role of regulatory T cells in immunological tolerance were recognized by this year’s Nobel Prize in Physiology or Medicine. We present here the unfolding of the Treg story, the players involved at various stages, and the explosive growth of knowledge about this fascinating cell population.

确立调节性T细胞在免疫耐受中的作用的开创性发现获得了今年的诺贝尔生理学或医学奖。我们在这里呈现Treg故事的展开，不同阶段的参与者，以及关于这个迷人细胞群的知识的爆炸性增长。

引用次数: 0

ATG9A-mediated autophagy prevents inflammatory skin disease by limiting TNFR1-driven STING activation and ZBP1-dependent cell death. atg9a介导的自噬通过限制tnfr1驱动的STING激活和zbp1依赖的细胞死亡来预防炎症性皮肤病。

IF 26.3 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-09 Epub Date: 2025-10-20 DOI: 10.1016/j.immuni.2025.09.019

Dario Priem, Jon Huyghe, Barbara Gilbert, Simon Verdonck, Tom Delanghe, Bruno Verstraeten, Esther Hoste, Peter Vandenabeele, Jonathan Maelfait, Geert van Loo, Mathieu J M Bertrand

Tumor necrosis factor (TNF) is a central pro-inflammatory cytokine with pathologic roles in chronic inflammatory and autoimmune disorders. The mechanisms by which TNF sensing drives the pathogenesis of these diseases are not fully understood. We previously showed that the lack of the autophagic lipid scramblase ATG9A in mouse keratinocytes leads to severe dermatitis and systemic inflammation, with features resembling human skin disorders. We now demonstrate that the disease is initiated by TNF but caused by cGAS/STING-dependent type I interferon (IFN) production and subsequent ZBP1-dependent apoptosis and necroptosis. ATG9A prevented the pathogenesis of the disease by engaging both light-chain 3 (LC3)-dependent and -independent autophagy. These results uncover an additional pathological arm of TNF signaling, opening avenues for alternative therapeutic interventions for TNF-driven diseases. Moreover, this study reveals another pathophysiological function of LC3-independent autophagy in restraining type I IFN production, which triggers the development or exacerbation of an interferonopathy in mice and humans.

肿瘤坏死因子（TNF）是一种中枢促炎细胞因子，在慢性炎症和自身免疫性疾病中具有病理作用。TNF感知驱动这些疾病发病机制的机制尚不完全清楚。我们之前的研究表明，小鼠角化细胞中缺乏自噬脂质合成酶ATG9A会导致严重的皮炎和全身性炎症，其特征与人类皮肤疾病相似。我们现在证明该疾病由TNF引发，但由cGAS/ sting依赖的I型干扰素（IFN）产生和随后的zbp1依赖的细胞凋亡和坏死坏死引起。ATG9A通过参与轻链3 （LC3）依赖性和非依赖性自噬来阻止疾病的发病机制。这些结果揭示了TNF信号的另一个病理分支，为TNF驱动疾病的替代治疗干预开辟了途径。此外，本研究揭示了lc3非依赖性自噬在抑制I型IFN产生方面的另一种病理生理功能，这种功能可触发小鼠和人类干扰素病的发展或恶化。

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引用次数: 0

Shape-shifting microglia respond to neuronal hyperexcitability 变形小胶质细胞对神经元的高兴奋性有反应

IF 32.4 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-09 DOI: 10.1016/j.immuni.2025.11.002

Clara Alice Musi, Diego Gomez-Nicola

The initial responses of microglia to neuronal stress or altered network activity are poorly characterized. Xie and colleagues show that during TDP-43-related neurodegeneration, microglia detect early neuronal hyperactivity and transition into a distinct rod-shaped state. This study uncovers a microglial state that precedes overt neuronal loss, shedding new light on the earliest stages of neurodegeneration.

小胶质细胞对神经元应激或网络活动改变的初始反应尚不清楚。Xie及其同事发现，在tdp -43相关的神经退行性变过程中，小胶质细胞检测到早期的神经元过度活跃，并转变为明显的杆状状态。这项研究揭示了明显的神经元丧失之前的小胶质细胞状态，为神经变性的早期阶段提供了新的线索。

引用次数: 0

Skin deep: Unconventional autophagy eats away TNF-driven skin inflammation. 皮肤深层：非常规的自噬消除了tnf驱动的皮肤炎症。

IF 26.3 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-09 DOI: 10.1016/j.immuni.2025.11.008

Ying Feng, Francis Ka-Ming Chan

Tumor necrosis factor (TNF), type I interferons (IFNs), and autophagy are important biological processes, but their interactions in inflammation have not been explored. In this issue of Immunity, Priem et al. reveal that ATG9A-mediated autophagy curbs skin inflammation by suppressing STING activation and Z-DNA binding protein 1 (ZBP1)-dependent cell death.

肿瘤坏死因子（TNF）、I型干扰素（ifn）和自噬是重要的生物学过程，但它们在炎症中的相互作用尚未被探索。在这一期的《免疫》杂志上，Priem等人发现atg9a介导的自噬通过抑制STING激活和Z-DNA结合蛋白1 （ZBP1）依赖性细胞死亡来抑制皮肤炎症。

引用次数: 0

The TCR-SUB1-DOCK2 axis promotes autoimmunity by driving pathogenic CD4+ T cell tissue infiltration TCR-SUB1-DOCK2轴通过驱动致病性CD4+ T细胞组织浸润来促进自身免疫

IF 32.4 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-09 DOI: 10.1016/j.immuni.2025.11.009

Xiaoxue Li, Wenhua Liang, Weifang Wang, Eilon Sherman, Keling Huang, Feng Wang

Aberrant tissue infiltration by activated CD4⁺ T cells is a central driver of autoimmunity, yet the molecular checkpoints governing antigen-specific T cell ingress remain poorly defined. We found that the transcription factor SUB1 was selectively upregulated in CD4⁺ T cells from individuals with autoimmune diseases. SUB1 expression was induced by the T cell receptor (TCR)-interferon regulatory factor 4 (IRF4) transcription factor axis. Conditional deletion of Sub1 in T cells reduced the expression of migration regulator dedicator of cytokinesis 2 (DOCK2), inhibited Rac-dependent actin polymerization and T cell motility, and prevented the onset of experimental autoimmune encephalomyelitis. Mechanistically, SUB1 underwent liquid-liquid phase separation to form biomolecular condensates that opened chromatin at the Junb and Dock2 loci. It then directly trans-activated Junb transcription and partnered with JUNB to amplify Dock2 transcription. Therefore, SUB1 is a critical gatekeeper of pathogenic T cell trafficking, and by linking TCR signaling to cytoskeletal remodeling, the TCR-SUB1-DOCK2 axis emerges as a tractable, migration-focused therapeutic target in autoimmune disorders.

活化的CD4+ T细胞异常组织浸润是自身免疫的核心驱动因素，然而控制抗原特异性T细胞进入的分子检查点仍然不明确。我们发现转录因子SUB1在自身免疫性疾病患者的CD4+ T细胞中选择性上调。SUB1表达由T细胞受体(TCR)-干扰素调节因子4 （IRF4）转录因子轴诱导。T细胞中条件缺失Sub1可降低迁移调节因子DOCK2的表达，抑制rac依赖性肌动蛋白聚合和T细胞运动，防止实验性自身免疫性脑脊髓炎的发生。从机制上讲，SUB1经过液-液相分离形成生物分子凝聚物，在Junb和Dock2位点打开染色质。然后它直接反式激活Junb转录，并与Junb合作扩增Dock2转录。因此，SUB1是致病性T细胞运输的关键守门者，通过将TCR信号与细胞骨架重塑联系起来，TCR-SUB1- dock2轴成为自身免疫性疾病中易于处理的、以迁移为重点的治疗靶点。

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引用次数: 0

Intestinal plasma cells get in formation 肠浆细胞得到信息

IF 32.4 1区医学 Q1 IMMUNOLOGY

Immunity

Pub Date : 2025-12-09 DOI: 10.1016/j.immuni.2025.11.017

Gabrielle R. Berman, Carla R. Nowosad

IgA plasma cells are the most abundant antibody-secreting reservoir in the body, yet details of their origin and behavior remain elusive. In this issue of Immunity, Simons et al. and Siniscalco et al. offer insights into IgA plasma cell dynamics during homeostasis and immunization.

IgA浆细胞是体内最丰富的抗体分泌库，但其起源和行为的细节仍然难以捉摸。在这一期的《免疫》杂志上，Simons等人和Siniscalco等人提供了在稳态和免疫过程中IgA浆细胞动力学的见解。

引用次数: 0

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