Cellular &Molecular Immunology最新文献_第10页

The membrane-associated ubiquitin ligases MARCH2 and MARCH3 target TIM-1 to limit Zika virus infection 膜相关泛素连接酶MARCH2和MARCH3靶向TIM-1以限制寨卡病毒感染。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-15 DOI: 10.1038/s41423-025-01334-2

Qi Zhang, Zhen-Wu Ma, Hui-Fang Li, Jia-Qing Zeng, Hong-Bing Shu, Shu Li

{"title":"The membrane-associated ubiquitin ligases MARCH2 and MARCH3 target TIM-1 to limit Zika virus infection","authors":"Qi Zhang, Zhen-Wu Ma, Hui-Fang Li, Jia-Qing Zeng, Hong-Bing Shu, Shu Li","doi":"10.1038/s41423-025-01334-2","DOIUrl":"10.1038/s41423-025-01334-2","url":null,"abstract":"T-cell immunoglobulin mucin family member-1 (TIM-1, also known as HAVCR1/KIM-1) is a transmembrane glycoprotein that has been reported to act as an entry receptor for multiple flaviviruses including Zika virus (ZIKV). The post-translational regulation of TIM-1 and its effects on ZIKV infection are unclear. In this study, we identified the membrane-associated RING-CH-type finger (MARCH) E3 ubiquitin ligase family members MARCH2 and MARCH3 as critical negative regulators of TIM-1 under physiological conditions. MARCH2 and MARCH3 associate with TIM-1 and mediate its K48-linked polyubiquitination at K338 and K346 respectively, leading to subsequent proteasomal degradation. While deficiency of either MARCH2 or MARCH3 modestly increases TIM-1 levels and enhances ZIKV infectivity, double knockout of MARCH2/3 has a more dramatic effect. Double knockout of MARCH2/3 increased ZIKV infectivity in wild-type but not TIM-1 knockout cells, and reconstitution of TIM-1K338R/K346R into TIM-1-deficient cells increases ZIKV infectivity to a higher degree than reconstitution with wild-type TIM-1. Knockout of either MARCH2 or MARCH3 increased ZIKV infectivity and pathogenesis in mice, whereas double knockout of MARCH2/3 has a more dramatic effect. These findings suggest that MARCH2 and MARCH3 target TIM-1 for K48-linked polyubiquitination and proteasomal degradation, thereby acting as redundant host restriction factors to limit ZIKV infection and pathogenesis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1032-1044"},"PeriodicalIF":19.8,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858989","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

Beyond the gut: decoding the gut–immune–brain axis in health and disease 超越肠道：解码健康和疾病中的肠道-免疫-大脑轴。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-14 DOI: 10.1038/s41423-025-01333-3

John Chulhoon Park, Leechung Chang, Ho-Keun Kwon, Sin-Hyeog Im

{"title":"Beyond the gut: decoding the gut–immune–brain axis in health and disease","authors":"John Chulhoon Park, Leechung Chang, Ho-Keun Kwon, Sin-Hyeog Im","doi":"10.1038/s41423-025-01333-3","DOIUrl":"10.1038/s41423-025-01333-3","url":null,"abstract":"Emerging research underscores the pivotal role of the gut–immune–brain axis, a dynamic bidirectional communication system involving intricate interactions between the gut microbiota, immune responses, and the central nervous system. Gut microbes and their metabolites have profound effects on immune and neurological homeostasis, influencing the development and function of multiple physiological systems. Disruption of the composition of the gut microbiota and barrier integrity has been implicated in various neurological and psychiatric disorders, including autism spectrum disorder, Alzheimer’s disease, Parkinson’s disease, depression, and anxiety. Most insights into these host–microbiota interactions come from preclinical models, revealing both the complexity and potential therapeutic opportunities of the gut–brain communication pathways. This review synthesizes the current understanding of these intricate interactions, exploring how microbiota-driven modulation of the gut and brain barriers, immune signaling, and neuronal pathways, such as those through the vagus nerve, contributes to health and disease. We further explore therapeutic implications, including personalized precision microbiota interventions, microbiome-derived biomarkers, and barrier-strengthening strategies. Advancing this field offers transformative potential for developing innovative, personalized therapies tailored to individual microbiomes and immune profiles, ultimately redefining clinical approaches to neurological and immune-mediated diseases.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 11","pages":"1287-1312"},"PeriodicalIF":19.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-025-01333-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The cytokine CSBF inhibits the IL-17A and TNF-α inflammatory pathways via SUSD2-ACT1 in keratinocytes and alleviates IMQ-induced psoriasis 细胞因子CSBF通过角化细胞中SUSD2-ACT1抑制IL-17A和TNF-α炎症通路，减轻imq诱导的银屑病。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-14 DOI: 10.1038/s41423-025-01325-3

Xixi Li, Kai Zhang, Xiulan Yang, Yingying Cheng, Sihua Huang, Weiwei Deng, Yuzhe Hu, Ting Li, Hongyu Duan, Xiaoning Mo, Jianrui Zhang, Ruoyu Li, Pingzhang Wang, Wenling Han

{"title":"The cytokine CSBF inhibits the IL-17A and TNF-α inflammatory pathways via SUSD2-ACT1 in keratinocytes and alleviates IMQ-induced psoriasis","authors":"Xixi Li, Kai Zhang, Xiulan Yang, Yingying Cheng, Sihua Huang, Weiwei Deng, Yuzhe Hu, Ting Li, Hongyu Duan, Xiaoning Mo, Jianrui Zhang, Ruoyu Li, Pingzhang Wang, Wenling Han","doi":"10.1038/s41423-025-01325-3","DOIUrl":"10.1038/s41423-025-01325-3","url":null,"abstract":"Overactivation of inflammatory signaling in keratinocytes is critical for psoriatic skin inflammation, but its regulatory mechanisms remain incompletely understood. Here, we demonstrate that the cytokine CSBF inhibits both individual and synergistic proinflammatory signaling induced by IL-17A and TNF-α (IL-17A/TNF-α) in keratinocytes, playing a protective role in psoriatic inflammation. The expression of CSBF was increased in the skin lesions and serum of psoriatic patients, and IL-17A/TNF-α enhanced its production. Csbf deletion exacerbated IMQ-induced psoriasis-like skin inflammation and led to hyperactivation of IL-17A/TNF-α signaling in keratinocytes. The CSBF protein significantly ameliorated psoriatic manifestations and suppressed IL-17A/TNF-α signaling through the receptor SUSD2. Mechanistically, CSBF-SUSD2 competed with TRAF6 and TNFR1 for interaction with ACT1, inhibiting the IL-17A/TNF-α signaling pathway. Overall, the anti-inflammatory cytokine CSBF has the potential to be a therapeutic option for psoriasis by targeting keratinocytes.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1109-1122"},"PeriodicalIF":19.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844725","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: Multiscale dynamic immunomodulation by a nanoemulsified Trojan-TLR7/8 adjuvant for robust protection against heterologous pandemic and endemic viruses 作者更正：纳米乳化特洛伊木马- tlr7 /8佐剂的多尺度动态免疫调节对异源大流行和地方性病毒的强大保护。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-08 DOI: 10.1038/s41423-025-01328-0

Yeon Jeong Yoo, Suhyeon Kim, Asha Wickramasinghe, Jaemoo Kim, JuA Song, Young-Il Kim, Juryeon Gil, Young-Woock Noh, Min-Ho Lee, Sang-Seok Oh, Myeong-Mi Lee, Yebin Seong, Jong-Soo Lee, Young Ki Choi, Yong Taik Lim

引用次数: 0

The gut microbiota in cancer immunity and immunotherapy 肠道微生物群在癌症免疫和免疫治疗中的作用。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-06 DOI: 10.1038/s41423-025-01326-2

Mingxu Xie, Xiang Li, Harry Cheuk-Hay Lau, Jun Yu

{"title":"The gut microbiota in cancer immunity and immunotherapy","authors":"Mingxu Xie, Xiang Li, Harry Cheuk-Hay Lau, Jun Yu","doi":"10.1038/s41423-025-01326-2","DOIUrl":"10.1038/s41423-025-01326-2","url":null,"abstract":"The human gastrointestinal tract harbors trillions of microorganisms, including bacteria, fungi, and viruses, to form the gut microbiota. Cumulative evidence has demonstrated the critical impact of gut microbes on cancer immunity. In cancer, an altered gut microbiota enriched with pathogenic bacteria can actively promote immune evasion and disrupt antitumor immunity, thereby supporting tumor growth and survival. Conversely, beneficial commensal bacteria (e.g., Lactobacillus and Bifidobacterium) have emerged as therapeutic probiotics for cancer prevention and as adjuvants for cancer therapy. The gut microbiota is also closely linked to the efficacy of immunotherapy. This review summarizes the effects of pathogenic bacteria and beneficial commensals, including T cells, B cells, natural killer cells, innate lymphoid cells, and myeloid-derived suppress cells, on various innate and adaptive immune cell populations in cancer. It also explores the mechanisms by which the gut microbiota influences immunotherapy efficacy, such as the modulation of innate immune cells and CD8+ T cells. Given its importance, an increasing number of studies have developed approaches to target the gut microbiota to improve immunotherapy outcomes and reduce immune-related adverse events. These strategies include antimicrobial intervention, probiotics, prebiotics/dietary modifications, microbial metabolites, phage therapy, and fecal microbiota transplantation. This review also evaluates clinical applications that use the gut microbiota to predict immunotherapy outcomes. Overall, the current understanding of host‒microbe interactions within the tumor microenvironment has laid a critical foundation for the translation of microbiota research into clinical practice, ultimately benefiting patients.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1012-1031"},"PeriodicalIF":19.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Provocation and palliation—the dual roles of dermal white adipose tissue in neutrophilic skin inflammation 激发和缓解-真皮白色脂肪组织在中性粒细胞皮肤炎症中的双重作用。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-06 DOI: 10.1038/s41423-025-01332-4

Sahiti Marella, Allison C. Billi

引用次数: 0

Immunoglobulin divalence promotes B-cell antigen receptor cluster scale-dependent functions 免疫球蛋白二价促进b细胞抗原受体簇规模依赖性功能。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-06 DOI: 10.1038/s41423-025-01327-1

Erdem Yilmaz, Amirmohammad Rahimi, Matthias Münchhalfen, Mihai Alevra, Arash Golmohammadi, Christian Tetzlaff, Felipe Opazo, Niklas Engels

{"title":"Immunoglobulin divalence promotes B-cell antigen receptor cluster scale-dependent functions","authors":"Erdem Yilmaz, Amirmohammad Rahimi, Matthias Münchhalfen, Mihai Alevra, Arash Golmohammadi, Christian Tetzlaff, Felipe Opazo, Niklas Engels","doi":"10.1038/s41423-025-01327-1","DOIUrl":"10.1038/s41423-025-01327-1","url":null,"abstract":"Antibodies, also known as immunoglobulins, share an evolutionarily conserved dimeric core structure with two antigen binding sites. However, recognition of foreign molecules can be achieved by monovalent binding domains, as evidenced by the T-cell antigen receptor and various innate immune receptors. Thus, the reason for the strict evolutionary conservation of immunoglobulin divalence remains unclear. In addition to being soluble immune effector molecules, each immunoglobulin is also expressed as a membrane-bound isoform in the context of the B-cell antigen receptor (BCR). Here, we generated monovalent BCRs and found that their signaling and antigen internalization capabilities were strongly impaired. By using advanced superresolution imaging of BCRs following stimulation with antigens of distinct valences, we showed that the receptor cluster scale in the plasma membrane determines the magnitude of intracellular signaling. The incorporation of additional ITAMs into single BCRs did not increase receptor sensitivity but caused cellular desensitization. Our results demonstrate that the BCR-controlled signaling machinery senses the clustering status of the BCR and that subtle changes in cluster sizes are translated into cellular responses. These findings improve our knowledge of adaptive immune receptor function and will aid in the design of synthetic chimeric antigen receptors.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1093-1108"},"PeriodicalIF":19.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PANoptosis in cancer: bridging molecular mechanisms to therapeutic innovations PANoptosis在癌症中的应用：连接分子机制与治疗创新。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-28 DOI: 10.1038/s41423-025-01329-z

Jin-Fei Lin, Ting-Ting Wang, Ren-Ze Huang, Yue-Tao Tan, Dong-Liang Chen, Huai-Qiang Ju

{"title":"PANoptosis in cancer: bridging molecular mechanisms to therapeutic innovations","authors":"Jin-Fei Lin, Ting-Ting Wang, Ren-Ze Huang, Yue-Tao Tan, Dong-Liang Chen, Huai-Qiang Ju","doi":"10.1038/s41423-025-01329-z","DOIUrl":"10.1038/s41423-025-01329-z","url":null,"abstract":"PANoptosis, a newly defined inflammatory programmed cell death, plays key roles in tumor development and progression. This process involves the assembly of PANoptosome complexes under various stimuli, which activate multiple cell death pathways simultaneously. By integrating key sensors and effector molecules, PANoptosis enhances immunogenic cell death while counteracts immune evasion mechanisms. This review focuses on current research of PANoptosis in cancer. Clinically, PANoptosis-related signatures show clinical value for predicting patient survival, discerning tumor immune microenvironment (TIME) characteristics and evaluating the therapeutic response. Mechanistically, complex signaling networks regulate PANoptosis, which in turn influences tumor behavior through dynamic interactions with TIME components. Therapeutically, targeting PANoptosis-related pathways, including nanomedicine approaches, demonstrate encouraging preclinical results. Particularly, combining PANoptosis modulation with radiotherapy, chemotherapy, or immunotherapy enhances anti-tumor efficacy. These findings position PANoptosis as a promising therapeutic target for reshaping TIME, overcoming treatment resistance, and improving cancer outcomes. Future research will focus on elucidating context-dependent PANoptosome regulation and translating these insights into precision oncology strategies.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"996-1011"},"PeriodicalIF":19.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myeloid cells in chronic liver inflammation 慢性肝脏炎症中的髓样细胞。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-28 DOI: 10.1038/s41423-025-01324-4

Dimitrios Patseas, Ahmed El-Masry, Zuobin Liu, Prakash Ramachandran, Evangelos Triantafyllou

引用次数: 0

Notch2−expressing CD4+ T cells attain immunoregulatory functions during autoimmune inflammation 表达notch2的CD4+ T细胞在自身免疫性炎症中获得免疫调节功能。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-07-23 DOI: 10.1038/s41423-025-01318-2

So-Eun Bae, Sang-Heon Park, Chae Youn Kim, Cho-Rong Lee, Chanyeon Lee, Rosah May Payumo, So Yeon Kim, Kyu-Young Sim, Ho Jin Kim, Hyungseok Seo, Seong-Joon Koh, Seunghee Hong, Sung-Gyoo Park

{"title":"Notch2−expressing CD4+ T cells attain immunoregulatory functions during autoimmune inflammation","authors":"So-Eun Bae, Sang-Heon Park, Chae Youn Kim, Cho-Rong Lee, Chanyeon Lee, Rosah May Payumo, So Yeon Kim, Kyu-Young Sim, Ho Jin Kim, Hyungseok Seo, Seong-Joon Koh, Seunghee Hong, Sung-Gyoo Park","doi":"10.1038/s41423-025-01318-2","DOIUrl":"10.1038/s41423-025-01318-2","url":null,"abstract":"Autoantigen−specific CD4+ T cells are central to the development of autoimmune diseases, while the expansion of regulatory T (Treg) cells expressing Forkhead box protein 3 (Foxp3) is essential for mitigating these conditions. In this study, we identified CD4+Notch2+Foxp3lo T cells in the spinal cords of mice with experimental autoimmune encephalomyelitis (EAE), dextran sodium sulfate−induced colitis model mice, and patients with ulcerative colitis as immune regulatory cells. These cells exhibited a nonproliferative, dysfunctional phenotype and demonstrated immune regulatory functions, including suppressive activity against activated CD4+ T cells and marked Treg cell expansion activity. Our data revealed that Notch2 deletion in Foxp3−expressing cells diminishes the ability of this population to reverse the clinical symptoms of EAE. Collectively, these findings suggest that Notch2 expression in dysfunctional CD4+ T cells plays a crucial role in immune regulation.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 9","pages":"1077-1092"},"PeriodicalIF":19.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0