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Shedding light on interventions for brain aging 揭示了大脑衰老的干预措施
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-10 DOI: 10.1016/j.immuni.2026.01.021
Juan Zhang, Qiang Liu
Immunotherapeutic approaches to brain aging remain largely preclinical and in early translational stages, and they have focused mostly on modulating innate immunity. In this issue of Immunity, Negredo et al. identify T cells bearing exhaustion-like signatures as a hallmark of brain aging and reveal the beneficial effects of an engineered IL-10 variant that functionally uncouples pro- and anti-inflammatory signaling in microglia.
脑衰老的免疫治疗方法仍主要停留在临床前和早期转化阶段,它们主要集中在调节先天免疫。在这一期的《免疫》杂志上,Negredo等人发现T细胞携带衰竭样信号是大脑衰老的标志,并揭示了一种工程IL-10变体的有益作用,该变体在功能上解耦了小胶质细胞中的促炎和抗炎信号。
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引用次数: 0
Influenza hijacks myeloid cells to inflict type-I interferon-fueled damage in the heart 流感劫持骨髓细胞,在心脏造成i型干扰素引发的损伤
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-09 DOI: 10.1016/j.immuni.2025.12.011
Jeffrey Downey, Ana Oliveira-Coelho, Máté G. Kiss, Gabriel Laghlali, Alexander Leunig, Emir Radkevich, Laszlo Halasz, Martin Umali, Joana Ferreira da Silva, Madeline L. Eller, Matteo Gianeselli, Magdalena M. Żak, Haley E. Randolph, Gabriel Caumartin, Wolfram C. Poller, Henrike Janssen, Laura L. Koekkoek, Jamshid Abdul-Ghafar, Pacific Huynh, Darwin D’Souza, Vladimir Roudko, Sheqouia Nauta, Jazz Munitz, Xisheng Li, Thomas Rathner, Ziche Chen, Anh Phan, Abigail Glick, Katarzyna Cialowicz, Zhihong Chen, Seunghee Kim-Schulze, Seonghun Yoon, Matthias Nahrendorf, Susmita Sahoo, Miriam Merad, Adolfo García-Sastre, Cameron S. McAlpine, Gustav J. Strijkers, Viviana Simon, Rachel Brody, Saurabh Mehandru, Zahi A. Fayad, Benjamin P. Kleinstiver, Lior Zangi, Mandy M.T. van Leent, Michael Schotsaert, Filip K. Swirski
Abundant evidence has correlated influenza infection with cardiovascular disease, yet mechanisms linking infection with the heart remain poorly understood. Here, we show that influenza infection damaged the human and murine heart. In mice, we showed that shortly after pulmonary infection, the virus infected a circulating myeloid pro-dendritic cell 3 (pro-DC3) that expressed high concentrations of the chemokine receptor CCR2. The heart, which produces abundant CCL2, preferentially attracted infected pro-DC3. In the myocardium, the virus escaped pro-DC3, infected cardiomyocytes, and triggered production of type-I interferon (IFN-I). Engagement of the IFN-I receptor (IFNAR1) on cardiomyocytes caused tissue damage and compromised heart function. Genetically and therapeutically dampening IFNAR1 exclusively in cardiomyocytes protected the heart while preserving anti-viral immunity in the lung. Our results identify a series of host-pathogen interactions that propagate tissue damage and uncover an axis for intervention to mitigate cardiovascular risk following viral infection.
大量证据表明流感感染与心血管疾病相关,但将感染与心脏联系起来的机制仍然知之甚少。在这里,我们证明流感感染损害了人类和小鼠的心脏。在小鼠中,我们发现在肺部感染后不久,病毒感染了表达高浓度趋化因子受体CCR2的循环髓系前树突状细胞3(前dc3)。产生大量CCL2的心脏优先吸引被感染的原dc3。在心肌中,病毒逃离原dc3,感染心肌细胞,并触发i型干扰素(IFN-I)的产生。IFN-I受体(IFNAR1)对心肌细胞的作用导致组织损伤和心功能受损。基因和治疗上抑制IFNAR1仅在心肌细胞中保护心脏,同时保持肺的抗病毒免疫。我们的研究结果确定了一系列宿主-病原体相互作用,这些相互作用会传播组织损伤,并揭示了一种干预轴,以减轻病毒感染后的心血管风险。
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引用次数: 0
Repression of RIPK1 kinase by INPP5D inhibits expression of diverse proinflammatory mediators and late-onset Alzheimer’s disease risk factors INPP5D抑制RIPK1激酶可抑制多种促炎介质和晚发性阿尔茨海默病危险因素的表达
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-02-02 DOI: 10.1016/j.immuni.2026.01.014
Xingxing Xie, Jianping Liu, Wei Liang, Yici Zhang, Xueqi Gong, Shenghao Yuan, Chunting Qi, Maoqing Huang, Linyu Shi, Meiling Hou, Mengmeng Zhang, Wei Liu, Weimin Sun, Yaqi Wu, Cui Li, Ze Cao, Hongyang Jing, Lihui Qian, Jingli Liu, Shufen Yuan, Qiong Wang, Yong Shen, Zhijun Liu, Yunxia Li, Heling Pan, Bing Zhu, Bing Shan, Kaiwen He, Wenyuan Wang, Chengyu Zou, Ying Li, James J. Chou, Junying Yuan
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引用次数: 0
Meningeal B cells: Emerging players at the brain border 脑膜B细胞:脑边界的新兴参与者
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-30 DOI: 10.1016/j.immuni.2026.01.013
Dianyu Chen, Heping Xu
The meninges, long viewed as passive protective membranes, are now recognized as active immunological interfaces harboring diverse immune populations. Among them, B cells have emerged as dynamic participants in central nervous system (CNS) homeostasis and disorders. Recent studies have identified distinct B cell subsets in the meninges at different developmental and activation stages, including precursors supported by skull marrow-derived progenitors and immunoglobulin A (IgA)⁺ plasma cells influenced by gut microbiota. These meningeal B cells contribute to immune tolerance, barrier protection, and potentially neural development and repair, while also exhibiting context-dependent pathogenic roles in CNS autoimmunity, aging, and neurodegeneration. In this review, we discuss the current knowledge of meningeal B cells and highlight key future research directions aimed at understanding their cellular dynamics, activation and differentiation processes, and the balance between protective and deleterious functions.
脑膜,长期以来被认为是被动的保护膜,现在被认为是活跃的免疫界面窝藏不同的免疫群体。其中,B细胞已成为中枢神经系统(CNS)稳态和失调的动态参与者。最近的研究已经确定了脑膜中处于不同发育和激活阶段的不同B细胞亚群,包括由颅骨骨髓源性祖细胞支持的前体和受肠道微生物群影响的免疫球蛋白A (IgA) +浆细胞。这些脑膜B细胞有助于免疫耐受、屏障保护和潜在的神经发育和修复,同时在中枢神经系统自身免疫、衰老和神经退行性变中也表现出环境依赖性的致病作用。在这篇综述中,我们讨论了目前对脑膜B细胞的认识,并强调了未来的重点研究方向,旨在了解其细胞动力学,激活和分化过程,以及保护和有害功能之间的平衡。
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引用次数: 0
Pre-existing neutralizing antibodies against cattle-transmitted influenza A virus H5N1 are detectable in unexposed individuals 在未暴露的个体中可检测到先前存在的针对牛传播的甲型流感病毒H5N1的中和抗体
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-30 DOI: 10.1016/j.immuni.2025.12.013
Katharina Daniel, Leon Ullrich, Denis Ruchnewitz, Matthijs Meijers, Nico Joel Halwe, Ursula Wild, Jan Eberhardt, Jacob Schön, Ricarda Stumpf, Maike Schlotz, Marie Wunsch, Luana Girao Lessa, Elsayed Mohammed Abdelwhab, Maryna Kuryshko, Christopher Dietrich, Andreas Pinger, Anna-Lena Schumacher, Maximilian Germer, Malena Rohde, Christian Kukat, Lutz Gieselmann, Henning Gruell, Donata Hoffmann, Martin Beer, Thomas Erren, Michael Lässig, Christoph Kreer, Florian Klein
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引用次数: 0
Stepwise epigenetic signal integration drives adaptive programming of cytotoxic lymphocytes 逐步表观遗传信号整合驱动细胞毒性淋巴细胞的适应性编程
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-30 DOI: 10.1016/j.immuni.2026.01.004
Simon Grassmann, Endi K. Santosa, Hyunu Kim, Isabelle B. Johnson, Adriana M. Mujal, Jean-Benoit LeLuduec, Sherry X. Fan, Mark Owyong, Adrian Straub, Liang Deng, Katharine C. Hsu, Dirk H. Busch, Colleen M. Lau, Joseph C. Sun
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引用次数: 0
Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition 针对老年大脑中的免疫细胞,揭示了工程细胞因子IL-10促进神经发生和改善认知
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-30 DOI: 10.1016/j.immuni.2026.01.016
Paloma Navarro Negredo, Justin You, Max Hauptschein, Adam B. Schroer, Daniel J. Richard, Gita C. Abhiraman, Andy P. Tsai, Eric D. Sun, Giulia Notarangelo, Julliana Ramirez-Matias, Olivia Y. Zhou, Matthew T. Buckley, Karen E. Malacon, Lucy Xu, Juliana Sucharov, Eduardo Ramirez Lopez, Lora Picton, Tony Wyss-Coray, Robert A. Saxton, Ricardo A. Fernandes, Saul A. Villeda, K. Christopher Garcia, Anne Brunet
The immune system could play an important role in the age-related decline in brain function, yet specific immune-based strategies to enhance brain resilience in older individuals are lacking. Here, we combined engineered proteins and direct brain delivery to target immune cell populations within the old brain. We detected T cells with an exhaustion signature in the old brain and targeted them with a potent engineered checkpoint inhibitor (RIPR-PD1). This led to T cell expansion and strong pro-inflammatory responses in many brain cell types, notably microglia. To rescue age-related inflammatory imbalances in microglia, we used the anti-inflammatory cytokine interleukin (IL)-10. IL-10 boosted anti-inflammatory responses in old microglia, but it also triggered pro-inflammatory signaling. An engineered IL-10 variant that uncouples pro- and anti-inflammatory responses positively impacted the transcriptome of multiple cell types, enhanced neurogenesis, and improved cognition in aged mice. Our findings pave the way for immunotherapies for the aged brain.
免疫系统可能在与年龄相关的脑功能衰退中发挥重要作用,但缺乏增强老年人大脑恢复能力的特定免疫策略。在这里,我们结合了工程蛋白和直接的大脑递送,以老年大脑中的免疫细胞群为目标。我们在老年大脑中检测到具有衰竭特征的T细胞,并用一种有效的工程检查点抑制剂(RIPR-PD1)靶向它们。这导致T细胞扩增和许多脑细胞类型,特别是小胶质细胞强烈的促炎反应。为了挽救小胶质细胞中与年龄相关的炎症失衡,我们使用了抗炎细胞因子白细胞介素(IL)-10。IL-10增强了老小胶质细胞的抗炎反应,但它也触发了促炎信号。一种工程化的IL-10变体可以解除促炎和抗炎反应的偶联,对多种细胞类型的转录组产生积极影响,增强神经发生,改善老年小鼠的认知能力。我们的发现为老年大脑的免疫疗法铺平了道路。
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引用次数: 0
B cell-intrinsic IL-2 signaling regulates inflammation by promoting IL-10 expression in CD25+ age-associated B cells B细胞内源性IL-2信号通过促进IL-10在CD25+年龄相关B细胞中的表达来调节炎症
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-30 DOI: 10.1016/j.immuni.2026.01.015
Juliette Gauthier, Maxime Maugendre, Simon Léonard, Yoni Desvois, Maïwenn Pineau, Romain Pinon, Nicolas Hipp, Karin Tarte, Patricia Amé, Sophie Hillion, Laure Michel, Céline Delaloy
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引用次数: 0
Commensal-myeloid crosstalk in neonatal skin regulates interleukin-1 signaling and cutaneous type 17 inflammation 新生儿皮肤的共生髓系串扰调节白细胞介素-1信号和皮肤17型炎症
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-29 DOI: 10.1016/j.immuni.2026.01.005
Miqdad O. Dhariwala, Ricardo O. Carale, Andrea M. DeRogatis, Henry Rodriguez-Valbuena, Joy N. Okoro, Christina A. Ekstrand, Antonin Weckel, Victoria M. Tran, Irek Habrylo, Rio Barrere-Cain, Oluwasunmisola T. Ojewumi, Allison E. Tammen, Jessica Tsui, Saba Shaikh, Shivaram Yellamilli, Ahmed K. Aladhami, Robin Schwartz, John M. Leech, Geil R. Merana, Kamir J. Hiam-Galvez, Matthias Mack, Joanna Halkias, James M. Gardner, Rachel L. Rutishauser, Gabriela K. Fragiadakis, Matthew H. Spitzer, Alexis J. Combes, Tiffany C. Scharschmidt
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引用次数: 0
A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages I型干扰素-线粒体轴调节巨噬细胞的efferocytosis和干扰素刺激基因诱导
IF 32.4 1区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-28 DOI: 10.1016/j.immuni.2025.12.010
Gillian Dunphy, Irene Adán-Barrientos, Irene Fernández-Delgado, Carolina Villarroya-Beltri, Ignacio Heras-Murillo, Elena Moya-Ruiz, Miguel Sánchez-Álvarez, Aitor Jarit-Cabanillas, Miguel A. del Pozo, Susana Guerra, Francisco Sánchez-Madrid, David Sancho
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引用次数: 0
期刊
Immunity
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