Current Opinion in Immunology最新文献

英文中文

Epigenetic regulation of inflammation dynamics during wound healing: a subtle yet profound shift in histone modifications 伤口愈合过程中炎症动态的表观遗传调控：组蛋白修饰的微妙而深刻的转变

IF 5.8 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-08-06 DOI: 10.1016/j.coi.2025.102635

Jingyu Xiao , Mengjiao Chen , Yamin Zhang , Juan Tao

Wound healing represents a dynamic process centered on the temporally coordinated inflammatory, proliferative, and remodeling phases. The inflammatory response exhibits a double-edged role: a moderate response is essential for normal healing, but excessive or persistent response impedes repair processes. In normal wound healing, histone modifications precisely regulate inflammatory responses from initiation to resolution, mainly manifested through early-stage modulation of NETs and late-stage intervention in macrophage polarization. In chronic non-healing wounds such as diabetic wounds, venous ulcers, and pressure ulcers, the specific pathological microenvironment regulates the inflammatory response of immune cells through various histone modifications, resulting in a greater intensity and longer duration of the inflammation. Herein, we summarize the critical roles of histone modifications in normal and chronic non-healing wounds, highlighting the subtle alterations of histone methylation and acetylation in macrophages that lead to macrophage reprogramming and inflammation regulation, thus providing the promise of precision therapy for chronic non-healing wounds.

伤口愈合是一个以时间协调的炎症、增殖和重塑阶段为中心的动态过程。炎症反应表现出双刃剑的作用：适度的反应对正常愈合至关重要，但过度或持续的反应会阻碍修复过程。在正常创面愈合过程中，组蛋白修饰精确调控炎症反应从开始到消退，主要表现在早期对NETs的调节和后期对巨噬细胞极化的干预。在糖尿病伤口、静脉溃疡、压疮等慢性不愈合伤口中，特定的病理微环境通过各种组蛋白修饰调节免疫细胞的炎症反应，导致炎症的强度更大、持续时间更长。在此，我们总结了组蛋白修饰在正常和慢性非愈合伤口中的关键作用，强调了巨噬细胞中组蛋白甲基化和乙酰化的细微变化导致巨噬细胞重编程和炎症调节，从而为慢性非愈合伤口的精确治疗提供了希望。

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引用次数: 0

Can we cure antiphospholipid syndrome? 我们能治愈抗磷脂综合征吗？

IF 5.8 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-08-06 DOI: 10.1016/j.coi.2025.102610

Pier Luigi Meroni , Enrico Capobianco , Francesco Tedesco

Antiphospholipid antibody syndrome (APS) is a vasculopathy with recurrent thrombosis and/or miscarriages mediated by autoantibodies against PL-binding proteins (aPL), mainly beta2glycoprotein I (β2GPI). While clotting is the key in vascular APS, thrombosis is not critical for placenta pathology. Despite that, anticoagulant/antiplatelet drugs are the leading treatments, but this is not a ‘one-size-fits-all’ therapy, and recurrences are reported. Additional therapies (e.g. antimalarials, statins) and a better characterization of the individual risk profile may improve the outcome. Nevertheless, we are still unable to ‘cure’ APS. The ideal target would be aPL suppression. However, immunosuppression or even B-cell therapies are not effective. Targeting CD38 on antibody-producing cells or anti-CD19 CAR-T cell therapy are promising alternatives, as well as the chimeric autoantigen receptor T cell therapy, due to the identification of β2GPI as an APS autoantigen. Further therapies aimed at improving clot lysis or affecting β2GPI/anti-β2GPI tissue complex formation are appealing preclinical perspectives.

抗磷脂抗体综合征（APS）是由针对pl结合蛋白（aPL）的自身抗体介导的复发性血栓形成和/或流产的血管病变，主要是β2糖蛋白I （β2GPI）。虽然凝血是血管APS的关键，但血栓形成不是胎盘病理的关键。尽管如此，抗凝血/抗血小板药物是主要的治疗方法，但这不是一种“一刀切”的治疗方法，并且有复发的报道。补充治疗（例如抗疟药、他汀类药物）和更好地描述个人风险状况可能会改善结果。然而，我们仍然无法“治愈”APS。理想的目标是抑制aPL。然而，免疫抑制甚至b细胞疗法都没有效果。由于β2GPI作为APS自身抗原的鉴定，靶向CD38抗体产生细胞或抗cd19 CAR-T细胞疗法以及嵌合自身抗原受体T细胞疗法都是有希望的替代方案。旨在改善凝块溶解或影响β2GPI/抗β2GPI组织复合物形成的进一步治疗具有吸引人的临床前前景。

引用次数: 0

Insights and perspectives into the discovery of complement-related biomarkers in cancer 在癌症中发现补体相关生物标志物的见解和观点

IF 5.8 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-08-06 DOI: 10.1016/j.coi.2025.102633

Daniel Ajona , Janire Debersaques , Ruben Pio

The complement system, a central component of innate immunity, is implicated in tumor biology, influencing processes such as tumor progression, immune evasion, and response to therapy. Numerous studies have identified alterations in complement effectors, activation products, regulatory proteins, and receptors in patients with cancer. These findings underscore the potential of complement-derived biomarkers for enhancing cancer diagnosis, prognosis, or treatment guidance across various oncology settings. However, despite substantial progress in discovery and early validation, no complement-related biomarker has yet been integrated into routine oncology practice. Key challenges in the field include the biological complexity of the complement system, variability in testing methods, and the lack of standardized protocols for sample collection, processing, and analysis. Addressing these issues is essential to ensure reliable and reproducible measurements. Moreover, the clinical utility of these biomarkers depends on their validation in real-world settings, as well as their integration with other molecular markers, advanced imaging, radiomics, and artificial intelligence tools. Advancing the development of harmonized assays and reference materials will be critical for the translation of complement biomarkers into clinical use in cancer. This review summarizes current knowledge on complement-related biomarkers in oncology, highlights technical and conceptual challenges, and discusses future directions to fully harness the potential of the complement system in cancer care.

补体系统是先天免疫的核心组成部分，与肿瘤生物学有关，影响肿瘤进展、免疫逃避和对治疗的反应等过程。许多研究已经确定了癌症患者体内补体效应物、激活产物、调节蛋白和受体的改变。这些发现强调了补体衍生的生物标志物在各种肿瘤学环境中增强癌症诊断、预后或治疗指导的潜力。然而，尽管在发现和早期验证方面取得了重大进展，但尚未有补体相关的生物标志物被纳入常规肿瘤学实践。该领域的主要挑战包括补体系统的生物学复杂性、测试方法的可变性以及缺乏样本收集、处理和分析的标准化协议。解决这些问题对于确保测量的可靠性和可重复性至关重要。此外，这些生物标记物的临床应用取决于它们在现实环境中的有效性，以及它们与其他分子标记物、先进成像、放射组学和人工智能工具的整合。推进统一的检测方法和参考物质的发展对于补体生物标志物在癌症中的临床应用至关重要。本文总结了目前肿瘤学中补体相关生物标志物的知识，强调了技术和概念上的挑战，并讨论了充分利用补体系统在癌症治疗中的潜力的未来方向。

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引用次数: 0

Red blood cell alloimmunization immunogenetic risk factor 红细胞异体免疫免疫遗传危险因素

IF 5.8 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-08-05 DOI: 10.1016/j.coi.2025.102634

Pascal Pedini , Jacques Chiaroni , Christophe Picard

Alloimmunization to blood group antigens is the result of a humoral immune response initiated by exposure to foreign antigens absent from the recipient's red blood cells (RBCs). Interestingly, not all individuals who receive mismatched RBC transfusions develop alloantibodies. Increasing evidence points to the role of the classical human leukocyte antigen (HLA) system in modulating this immune response. More recently, polymorphisms in nonclassical HLA molecules have been implicated in the regulation of inflammatory responses, particularly in patients with sickle cell disease. The role of natural fetomaternal microchimerism may also be a factor to consider in explaining individual variability in alloimmune response.

The genetic diversity of both RBC antigens and HLA across ethnic groups underscores the need for high-throughput sequencing technologies to improve donor–recipient matching. In the future, genotyping strategies should aim not only to assess individual risk for alloantibody development but also to guide the selection of compatible RBC units, thereby reducing the likelihood of alloimmunization.

对血型抗原的同种免疫是由暴露于受体红细胞（rbc）中缺失的外来抗原而引起的体液免疫反应的结果。有趣的是，并非所有接受不匹配红细胞输血的个体都会产生同种抗体。越来越多的证据表明经典的人类白细胞抗原（HLA）系统在调节这种免疫反应中的作用。最近，非经典HLA分子的多态性与炎症反应的调节有关，特别是在镰状细胞病患者中。自然胎母微嵌合的作用也可能是解释同种免疫反应个体差异的一个考虑因素。不同种族的红细胞抗原和HLA的遗传多样性强调了需要高通量测序技术来改善供体-受体匹配。未来，基因分型策略的目标不仅是评估个体产生同种异体抗体的风险，还应指导选择相容的红细胞单位，从而降低同种异体免疫的可能性。

引用次数: 0

The role of epigenetics in inflammatory memory 表观遗传学在炎症记忆中的作用。

IF 5.8 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-08-04 DOI: 10.1016/j.coi.2025.102630

Yaqin Yu , Yueqi Qiu , Ming Zhao

Inflammatory memory refers to the ability of an organism to mount a stronger or faster response upon re-exposure to similar inflammatory stimuli. This heightened sensitivity was once thought to be a unique characteristic of immune cells. However, recent studies have challenged this traditional view, revealing that inflammatory memory is a widely prevalent phenomenon that extends beyond immune cells to include nonimmune cells. These studies indicate that the formation and maintenance of inflammatory memory largely depend on the regulation of epigenetics. Epigenetics involves heritable changes in gene expression without altering the DNA sequence, including mechanisms such as DNA methylation and histone modifications. These modifications regulate gene transcription and influence the cellular response to inflammatory stimuli. In this review, we will discuss the epigenetic mechanisms of inflammatory memory in both immune and nonimmune cells, focusing on new mechanistic insights from the past few years, and briefly discuss the unknowns and future strategies.

炎症记忆是指生物体在再次暴露于类似的炎症刺激时产生更强或更快反应的能力。这种高度的敏感性曾被认为是免疫细胞的独特特征。然而，最近的研究已经挑战了这一传统观点，揭示炎症记忆是一种广泛存在的现象，它延伸到免疫细胞以外的非免疫细胞。这些研究表明炎症记忆的形成和维持在很大程度上依赖于表观遗传学的调控。表观遗传学涉及在不改变DNA序列的情况下基因表达的遗传变化，包括DNA甲基化和组蛋白修饰等机制。这些修饰调节基因转录并影响细胞对炎症刺激的反应。在这篇综述中，我们将讨论免疫和非免疫细胞炎症记忆的表观遗传机制，重点关注过去几年来新的机制见解，并简要讨论未知和未来的策略。

引用次数: 0

Immunological complications of blood transfusion: current insights and advances 输血的免疫学并发症：当前的见解和进展

IF 5.8 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-07-29 DOI: 10.1016/j.coi.2025.102617

Naveen Bansal , Manish Raturi , Charu Singh , Yashik Bansal

Blood transfusion is integral to modern medicine but carries significant immunological risks. This review outlines key immune-mediated complications, including acute hemolytic transfusion reactions from ABO incompatibility, and febrile nonhemolytic reactions caused by cytokines or antileukocyte antibodies. Other reactions include allergic responses, anaphylaxis (notably in IgA-deficient patients), and transfusion-related acute lung injury — the leading cause of transfusion-related mortality. Delayed hemolytic reactions, alloimmunization-induced platelet refractoriness, transfusion-associated graft-versus-host disease, and post-transfusion purpura also contribute to morbidity. Transfusion-related immunomodulation may increase infection and cancer recurrence risks. Preventive measures such as leukoreduction, irradiation, extended antigen matching, and restrictive transfusion strategies are crucial. This review article emphasis the importance on the need for strict adherence to protocols, enhanced hemovigilance, and education, especially in resource-limited settings. This review article summarizes the various immunological complications of blood transfusion and the recent advances in their etiopathogenesis, prevention, mitigation, and future research direction.

输血是现代医学不可或缺的一部分，但也会带来重大的免疫风险。这篇综述概述了主要的免疫介导的并发症，包括ABO不相容引起的急性溶血性输血反应，以及由细胞因子或抗白细胞抗体引起的发热性非溶血性反应。其他反应包括过敏反应、过敏反应（特别是iga缺乏患者）和输血相关的急性肺损伤（输血相关死亡的主要原因）。延迟溶血反应、同种异体免疫诱导的血小板难治性、输血相关的移植物抗宿主病和输血后紫癜也有助于发病率。输血相关的免疫调节可能增加感染和癌症复发的风险。预防措施，如白细胞诱导、照射、扩大抗原匹配和限制性输血策略是至关重要的。这篇综述文章强调了严格遵守协议、加强血液警戒和教育的重要性，特别是在资源有限的情况下。本文综述了输血引起的各种免疫并发症及其发病机制、预防、缓解和未来研究方向等方面的最新进展。

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引用次数: 0

Can we cure vasculitis? 我们能治愈血管炎吗？

IF 5.8 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-07-28 DOI: 10.1016/j.coi.2025.102618

Meghan E Free , Dominic J Ciavatta , Ronald J Falk

As with all autoimmune diseases, antineutrophil cytoplasmic autoantibody (ANCA) vasculitis cannot be cured by a singular approach. This complexity arises because autoimmune conditions typically result from multiple hits to the immune system — including genetic predisposition, environmental exposures, infections, and perturbations in adaptive and innate immunity. However, these multiple hits also offer opportunities to develop targeted, multipronged strategies aimed at achieving lasting remission or even cure. The field of ANCA vasculitis is unique because a subset of patients has successfully discontinued immunosuppression while maintaining remission. This challenges the long-standing belief and paradigm that autoimmunity necessitates lifelong immunosuppression therapy characterized by cycles of relapse and remission. These patients embody the potential for cure. By exploring theoretical pathways — such as early intervention to modulate innate immunity, restoring normal autoantigen production, enhancing immunoregulatory mechanisms, and eliminating autoreactive cells — we can begin to chart a detailed molecular and cellular roadmap. This approach aims to develop combination therapies that restore immune balance and ultimately transform the management of autoimmune vasculitis, moving toward the goal of durable remission and cure.

与所有自身免疫性疾病一样，抗中性粒细胞胞浆自身抗体（ANCA）血管炎不能通过单一的方法治愈。这种复杂性的出现是因为自身免疫性疾病通常是由免疫系统的多重打击引起的，包括遗传易感性、环境暴露、感染以及适应性和先天免疫的扰动。然而，这些多重打击也为开发有针对性的、多管齐下的战略提供了机会，旨在实现持久的缓解甚至治愈。ANCA血管炎领域是独特的，因为一部分患者在维持缓解的同时成功地停止了免疫抑制。这挑战了长期以来的信念和范式，即自身免疫需要以复发和缓解周期为特征的终身免疫抑制治疗。这些病人体现了治愈的潜力。通过探索理论途径——如早期干预来调节先天免疫，恢复正常的自身抗原产生，增强免疫调节机制，消除自身反应性细胞——我们可以开始绘制详细的分子和细胞路线图。该方法旨在开发恢复免疫平衡的联合疗法，并最终改变自身免疫性血管炎的管理，朝着持久缓解和治愈的目标迈进。

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引用次数: 0

Complement system modulation in age-related macular degeneration: navigating failures, building future successes 补体系统调节在年龄相关性黄斑变性：导航失败，建立未来的成功

IF 5.8 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-07-28 DOI: 10.1016/j.coi.2025.102616

Aliénor Vienne-Jumeau , Elodie Bousquet , Francine Behar-Cohen

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in elderly populations across developed countries. Complement system dysregulation has been implicated in AMD onset and evolution. Complement inhibition therapies have been authorized in the USA as the primary treatment for geographic atrophy, the dry form of AMD. They have shown moderate efficacy in slowing geographic atrophy lesion growth but have not demonstrated improvements in visual function. Challenges remain, including the optimal timing of intervention, delivery routes, safety concerns, the lack of sensitive biomarkers to assess efficacy and guide patient selection, and variability in therapeutic response.

Complement modulation represents a promising yet complex therapeutic avenue in AMD. Future success will require earlier intervention, precision medicine approaches integrating genetic and imaging biomarkers, and the exploration of combination or gene-based therapies.

年龄相关性黄斑变性（AMD）是发达国家老年人不可逆中央视力丧失的主要原因。补体系统失调与AMD的发病和进化有关。补体抑制疗法已被批准在美国作为主要治疗地理萎缩，干型AMD。它们在减缓地理萎缩病变的生长方面显示出中等疗效，但在视觉功能方面没有表现出改善。挑战仍然存在，包括干预的最佳时机、递送路线、安全性问题、缺乏敏感的生物标志物来评估疗效和指导患者选择，以及治疗反应的可变性。补体调节是一种有前景但复杂的AMD治疗途径。未来的成功将需要更早的干预，整合遗传和成像生物标志物的精准医学方法，以及探索组合或基于基因的治疗方法。

引用次数: 0

Friend or foe? — Janus Langerhans cells in skin immunity and promising clinical application 是敌是友？-朗格汉斯细胞在皮肤免疫中的应用前景

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-07-18 DOI: 10.1016/j.coi.2025.102615

Mengjiao Chen , Shiyi Yan , Jun Li , Juan Tao

Langerhans cells (LCs), the professional antigen-presenting cells in the epidermis, serve as the first line of defense in the skin's immune system. With advancements in detection technologies and the development of diverse animal models, LCs have been shown to exhibit heterogeneous origins, phenotypes, and functions, which are regulated in a context-dependent manner by various cytokines and transcription factors. This heterogeneity enables LCs to either promote or suppress immune responses depending on the microenvironment. As research advances in elucidating the regulatory mechanisms underlying LC phenotypes and functions across various pathological conditions, clinical studies targeting LCs are gradually progressing. This review summarizes commonly used experimental animal models in LC research, highlights the phenotypic diversity of LCs in various diseases, and discusses their dual roles in disease progression. With our understanding of LC heterogeneity deepening, we anticipate elucidating the characteristic of distinct LC subgroups, thereby establishing a solid foundation for LC-targeted precision immunotherapy.

朗格汉斯细胞（LCs）是表皮中的专业抗原呈递细胞，是皮肤免疫系统的第一道防线。随着检测技术的进步和多种动物模型的发展，lc已被证明具有异质的起源、表型和功能，并受各种细胞因子和转录因子的环境依赖方式调节。这种异质性使LCs能够根据微环境促进或抑制免疫反应。随着研究在阐明不同病理条件下LC表型和功能的调控机制方面的进展，针对LC的临床研究也在逐步进行。本文综述了LC研究中常用的实验动物模型，强调了LC在各种疾病中的表型多样性，并讨论了它们在疾病进展中的双重作用。随着我们对LC异质性认识的加深，我们期望阐明不同LC亚群的特征，从而为LC靶向精确免疫治疗奠定坚实的基础。

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引用次数: 0

Neuroimmune mechanisms of neuropsychiatric systemic lupus erythematosus 神经精神系统性红斑狼疮的神经免疫机制

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-07-18 DOI: 10.1016/j.coi.2025.102608

Stacie L Lin , Michael C Carroll

In systemic lupus erythematosus (SLE), chronic autoimmunity and sustained inflammation can lead to the development of neuropsychiatric lupus (NPSLE) in up to 80% of patients. Elevated interferon-alpha (IFNα) is detected in serum and cerebrospinal fluid, making it a major focus in studies investigating the mediators of NPSLE. Others have emphasized the role of autoantibodies, such as anti-dsDNA, which have been shown to cross-react with neurotransmitter receptors and directly damage neurons. In this review, we present an integrative framework in which immune complexes deposited in the neurovasculature trigger local IFNα production in the brain. We discuss how complement activation amplifies inflammation by recruiting monocytes and promoting transcriptional shifts in glial cells toward reactive and neurotoxic states. Together, cellular and soluble immune effectors converge to disrupt neuronal function and drive the behavioral symptoms characteristic of NPSLE.

在系统性红斑狼疮（SLE）中，慢性自身免疫和持续炎症可导致高达80%的患者发展为神经精神性狼疮（NPSLE）。血清和脑脊液中检测到干扰素α (IFNα)升高，使其成为研究NPSLE介质的主要焦点。其他人强调自身抗体的作用，如抗dsdna，已被证明与神经递质受体交叉反应并直接损伤神经元。在这篇综述中，我们提出了一个综合框架，其中沉积在神经血管中的免疫复合物触发大脑中局部IFNα的产生。我们讨论了补体激活如何通过募集单核细胞和促进神经胶质细胞向反应性和神经毒性状态的转录转变来放大炎症。细胞和可溶性免疫效应物聚集在一起，破坏神经元功能并驱动NPSLE特征的行为症状。

引用次数: 0

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