Cellular &Molecular Immunology最新文献

The role of exosomes in immunopathology and potential therapeutic implications. 外泌体在免疫病理中的作用及其潜在的治疗意义。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-14 DOI: 10.1038/s41423-025-01323-5

Wenhui Wang, Shuya Qiao, Xianghui Kong, Gensheng Zhang, Zhijian Cai

{"title":"The role of exosomes in immunopathology and potential therapeutic implications.","authors":"Wenhui Wang, Shuya Qiao, Xianghui Kong, Gensheng Zhang, Zhijian Cai","doi":"10.1038/s41423-025-01323-5","DOIUrl":"https://doi.org/10.1038/s41423-025-01323-5","url":null,"abstract":"Extracellular vesicles (EVs), including exosomes, ectosomes, and apoptotic bodies, are released by various cells. Among these subtypes, exosomes have been extensively studied and demonstrated to be crucial mediators of intercellular communication involving multiple physiological and pathological processes. Four primary steps influence the biogenesis of exosomes: generation of early endosomes, formation and maturation of multivesicular bodies (MVBs), MVB and plasma membrane fusion for exosome release, and MVB fusion with lysosomes for degradation. During the formation and maturation of MVBs, the main effector molecules, such as RNAs and proteins, are sorted into exosomes via diverse mechanisms. However, the effector molecules of exosomes are dynamic and reflect cell states in real time. Therefore, exosomes secreted by cells under disease conditions are often pathogenic. This review focuses on recent advances in the understanding of exosome biogenesis and the immunopathological effects of exosomes. In addition, potential strategies to mitigate the pathological effects of exosomes are summarized in this review.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD8⁺GZMK⁺CD27⁺CCR7⁺ T cells mobilized by splenic sympathetic nerves aggravate brain ischemia‒reperfusion injury via CCL19-positive endothelial cells. 脾交感神经动员CD8+GZMK+CD27+CCR7+ T细胞通过ccl19阳性内皮细胞加重脑缺血再灌注损伤。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-14 DOI: 10.1038/s41423-025-01311-9

Ying Bai, Hui Ren, Shuo Leng, Mengqin Yuan, YiXin Jiang, Shenyang Zhang, Yu Wang, Minzi Ju, Zhi Wang, Wen Xi, Lian Xu, Bingjing Zheng, Daxing Li, Xinchen Huo, Tianhao Zhu, Beicheng Zhang, Ling Shen, Yuan Zhang, Wei Jiang, John H Zhang, Bing Han, Honghong Yao

{"title":"CD8+GZMK+CD27+CCR7+ T cells mobilized by splenic sympathetic nerves aggravate brain ischemia‒reperfusion injury via CCL19-positive endothelial cells.","authors":"Ying Bai, Hui Ren, Shuo Leng, Mengqin Yuan, YiXin Jiang, Shenyang Zhang, Yu Wang, Minzi Ju, Zhi Wang, Wen Xi, Lian Xu, Bingjing Zheng, Daxing Li, Xinchen Huo, Tianhao Zhu, Beicheng Zhang, Ling Shen, Yuan Zhang, Wei Jiang, John H Zhang, Bing Han, Honghong Yao","doi":"10.1038/s41423-025-01311-9","DOIUrl":"https://doi.org/10.1038/s41423-025-01311-9","url":null,"abstract":"Splenic sympathetic activity critically modulates peripheral immunity after ischemic stroke, thus intervention in spleen sympathetic activity represents a promising therapeutic strategy for stroke. However, the mechanisms underlying spleen-brain-immune axis communication remain poorly understood. Here, we utilized a surgical denervation protocol to perform splenic sympathetic denervation (SDN), which significantly attenuated brain injury following stroke. Through single-cell RNA sequencing, we identified a novel GZMK+CD8+CD27+CCR7+ T-cell subset in patients with acute ischemic stroke (AIS), which we designated stroke-associated T (Tsa) cells. The expansion of Tsa cells was positively correlated with the severity of clinical symptoms and was driven by the splenic sympathetic nervous system. Stroke-induced sympathetic activation triggers the release of splenic norepinephrine (NE), which preferentially signals through ADRB2 on Tsa cells to promote their mobilization. Additionally, ischemic injury induces endothelial cell-specific expression of CCL19, which chemoattracts Tsa cells into the brain parenchyma via their cognate CCR7 receptor, exacerbating neuroinflammatory injury and neurological deficits in a transient middle cerebral artery occlusion (tMCAO) mouse model. We developed a CCR7-targeting peptide to disrupt this chemotactic axis and reduce T-cell infiltration, thereby mitigating brain injury. Our findings highlight SDN as a promising therapeutic strategy to attenuate ischemia‒reperfusion injury and suggest its potential as an adjunctive therapy for reperfusion treatment in AIS patients.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-17-secreting γδ T-cell-driven Siglec-F⁺ neutrophils mediate lung pathology in emphysema. 分泌il -17的γδ t细胞驱动的Siglec-F+中性粒细胞介导肺气肿的肺病理。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-11 DOI: 10.1038/s41423-025-01322-6

Kingston H G Mills

引用次数: 0

Cholesterol promotes autoimmune pathology through T follicular helper cells. 胆固醇通过T滤泡辅助细胞促进自身免疫病理。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-10 DOI: 10.1038/s41423-025-01319-1

Wei Li, George C Tsokos

引用次数: 0

Beyond T-cell subsets: stemness and adaptation redefining immunity and immunotherapy. 超越t细胞亚群：干细胞和适应性重新定义免疫和免疫治疗。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-10 DOI: 10.1038/s41423-025-01321-7

Dawei Zou, Xian C Li, Wenhao Chen

{"title":"Beyond T-cell subsets: stemness and adaptation redefining immunity and immunotherapy.","authors":"Dawei Zou, Xian C Li, Wenhao Chen","doi":"10.1038/s41423-025-01321-7","DOIUrl":"https://doi.org/10.1038/s41423-025-01321-7","url":null,"abstract":"T cells often acquire diverse phenotypes and functional states following activation. CD4+ T cells are traditionally classified into distinct effector subsets, such as Th1, Th2, Th17, and Tfh, on the basis of their cytokine profiles and functional roles. While this framework has advanced our understanding of adaptive immunity, it has limitations in explaining the persistence of T-cell responses in settings of autoimmunity and transplant rejection, in contrast to its limited efficacy in cancer. Moving beyond this subset-based framework, recent studies have revealed that stemness and adaptation are fundamental to CD4+ T-cell fate and function. Central to this new understanding is the TCF1+ stem-like CD4+ T-cell population, which emerges early after activation and serves as a reservoir for effector differentiation. These cells dynamically integrate environmental cues to direct effector differentiation and shape functional outcomes at target tissue sites, a process we define as clonal adaptation. By balancing self-renewal with effector differentiation, stem-like CD4+ T cells continue to replenish short-lived effector cells to sustain autoimmunity, transplant rejection, chronic infections, and allergic diseases. However, under tolerogenic conditions or within the tumor microenvironment, these cells often fail to differentiate into effectors, instead entering dysfunctional states or regulatory T-cell differentiation. Targeting stem-like CD4+ T cells offers great therapeutic potential: disrupting their persistence could mitigate autoimmune pathology and transplant rejection, whereas enhancing their effector capacity could improve antitumor immunity.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monocyte-derived TGF-β shapes memory CD8+ T cells. 单核细胞来源的TGF-β塑造记忆性CD8+ T细胞。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-10 DOI: 10.1038/s41423-025-01317-3

Mohammad H Hasan, Lalit K Beura

引用次数: 0

Eliciting antitumor immunity via therapeutic cancer vaccines. 通过治疗性癌症疫苗激发抗肿瘤免疫。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-09 DOI: 10.1038/s41423-025-01316-4

Kun Peng, Xiaoxue Zhao, Yang-Xin Fu, Yong Liang

{"title":"Eliciting antitumor immunity via therapeutic cancer vaccines.","authors":"Kun Peng, Xiaoxue Zhao, Yang-Xin Fu, Yong Liang","doi":"10.1038/s41423-025-01316-4","DOIUrl":"10.1038/s41423-025-01316-4","url":null,"abstract":"Therapeutic cancer vaccines aim to expand and activate antigen-specific T cells for the targeted elimination of cancer cells. While early clinical trials faced challenges due to suboptimal antigen-specific T-cell activation, recent advancements in antigen discovery and vaccine platform engineering have revitalized the field. This review provides a comprehensive overview of key tumor antigens, including tumor-associated antigens, viral oncoprotein antigens, neoantigens, and cryptic antigens, with a focus on their immunogenicity and therapeutic potential. Advances in our understanding of traditional cancer vaccination targets, in conjunction with the timely identification of novel antigen epitopes, have facilitated the strategic selection of vaccination targets. We also discuss the evolution of cancer vaccine platforms-spanning peptide-based formulations to advanced mRNA vectors-emphasizing innovative strategies to optimize antigen delivery efficiency and adjuvant effects. Efficient antigen delivery and adjuvant selection overcome immune tolerance and tumor-induced immunosuppression. Furthermore, we examine recent clinical trial data and emerging combination approaches that integrate cancer vaccines with other immunotherapies to increase efficacy. While significant progress has been made, challenges remain in improving vaccine-induced T-cell responses, overcoming immune suppression, and translating these advances into effective clinical interventions. Addressing these hurdles will be critical for realizing the full potential of cancer vaccines in immunotherapy.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Three macrophage subsets are identified in the uterus during early human pregnancy. 作者更正：在人类妊娠早期子宫中发现了三种巨噬细胞亚群。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-08 DOI: 10.1038/s41423-025-01320-8

Xiangxiang Jiang, Mei-Rong Du, Min Li, Hongmei Wang

引用次数: 0

CD2 augmentation enhances CAR-T-cell efficacy via immunological synapse remodeling and T-cell exhaustion mitigation. CD2增强通过免疫突触重塑和t细胞衰竭缓解增强car - t细胞效能。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-04 DOI: 10.1038/s41423-025-01314-6

Qi Zhu, Jiajia Li, Nan Liu, Lu Han, Zhiqiang Wu, Yao Wang, Xin Lin, Jianshu Wei, Weidong Han

引用次数: 0

Metabolic reprogramming via FOXP3 engineering: A Novel strategy to enhance CAR-T cell efficacy in solid tumors. 通过FOXP3工程进行代谢重编程：一种增强CAR-T细胞在实体肿瘤中的疗效的新策略。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-03 DOI: 10.1038/s41423-025-01315-5

Dan Li, Siyuan Qiang, Bin Li

引用次数: 0