Cellular &Molecular Immunology最新文献_第2页

Gut-derived indole propionic acid alleviates liver fibrosis by targeting profibrogenic macrophages via the gut‒liver axis. 肠源性吲哚丙酸通过肠-肝轴靶向促纤维化巨噬细胞减轻肝纤维化。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-09-08 DOI: 10.1038/s41423-025-01339-x

Yuanyuan Luo, Yarong Hao, Chunyan Sun, Zhi Lu, Hao Wang, Yuhan Lin, Yaping Guan, Lingyan Cai, Chenhong Ding, Binbin Li, Fei Chen, Yiting Lu, Yong Lin, Xin Zeng

{"title":"Gut-derived indole propionic acid alleviates liver fibrosis by targeting profibrogenic macrophages via the gut‒liver axis.","authors":"Yuanyuan Luo, Yarong Hao, Chunyan Sun, Zhi Lu, Hao Wang, Yuhan Lin, Yaping Guan, Lingyan Cai, Chenhong Ding, Binbin Li, Fei Chen, Yiting Lu, Yong Lin, Xin Zeng","doi":"10.1038/s41423-025-01339-x","DOIUrl":"https://doi.org/10.1038/s41423-025-01339-x","url":null,"abstract":"Gut-derived metabolites are essential for liver fibrogenesis. The aim of this study was to determine the alteration of indole-3-propionic acid (IPA), a crucial tryptophan metabolite, in liver fibrosis and delineate the roles of enterogenic IPA in fibrogenesis. In the present study, metabolomics assays focused on tryptophan metabolism were applied to explore the decreased levels of IPA in the feces and serum of cirrhotic patients, as well as in the feces and portal vein serum of fibrotic mice. Oral IPA administration exerted strong antifibrotic effects with favorable biosafety in three fibrotic models via multicellular modulation. Multiplex immunohistochemical staining and DAOSLIMIT imaging demonstrated that gut-derived IPA was directly captured by hepatic macrophages. Macrophage-specific AhR knockout blocked the antifibrotic effect of IPA, while the therapeutic efficacy was maintained in mice with HSC- or hepatocyte-specific AhR depletion. Furthermore, IPA governed macrophage recruitment, S100A8/A9+ phenotype transformation and profibrotic and proinflammatory functions, resulting in amelioration of hepatic fibrogenesis. Mechanistically, IPA targeted the AhR/NF-κB/S100A8/A9 axis and AhR/SPHK2/S1P signaling to inhibit the profibrotic biological characteristics of macrophages and subsequently interrupted the profibrogenic crosstalk between macrophages and hepatic stellate cells (HSCs) in coculture systems and 3D liver spheroid models. These findings increase the understanding of the effects of enterogenic tryptophan metabolites on liver fibrogenesis via the gut‒liver axis and support the translational potential of IPA. By targeting profibrogenic macrophages, IPA could serve as a promising candidate for the clinical management of liver fibrosis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029060","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

Macrophage-derived VISTA engages with LRIG1 and hinders gut epithelial repair in colitis. 巨噬细胞来源的VISTA参与LRIG1并阻碍结肠炎的肠上皮修复。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-29 DOI: 10.1038/s41423-025-01338-y

Mengyuan Li, Binfeng Chen, Zhixiong Wang, Ruixiang Guo, Ningjing Xiong, Yichao Qian, Baokui Ye, Yimei Lai, Shuyi Wang, Yijun Zhu, Niansheng Yang, Hui Zhang

{"title":"Macrophage-derived VISTA engages with LRIG1 and hinders gut epithelial repair in colitis.","authors":"Mengyuan Li, Binfeng Chen, Zhixiong Wang, Ruixiang Guo, Ningjing Xiong, Yichao Qian, Baokui Ye, Yimei Lai, Shuyi Wang, Yijun Zhu, Niansheng Yang, Hui Zhang","doi":"10.1038/s41423-025-01338-y","DOIUrl":"https://doi.org/10.1038/s41423-025-01338-y","url":null,"abstract":"Disruption of the intestinal epithelial barrier and incomplete repair are critical for the development of colitis. V-domain immunoglobulin domain suppressor of T-cell activation (VISTA), encoded by Vsir, functions as an immune checkpoint. In the present work, we report that VISTA is predominantly upregulated in macrophages from patients with inflammatory bowel disease (IBD) and in mice with dextran sulfate sodium (DSS)-induced colitis. VISTA deficiency or blockade ameliorates DSS-induced colitis severity. Epithelial damage is notably less severe in Vsir-/-Rag1-/- mice than in Vsir+/+Rag1-/- mice. Intriguingly, macrophage depletion eliminates disease severity differences between Vsir-/- and wild-type (WT) mice. Vsir ablation does not alter cytokine profiles or macrophage differentiation but alleviates macrophage-mediated epithelial injury, as Vsir-/- macrophage transfer induces milder damage than WT macrophage transfer does. Interestingly, Vsir-/- mice exhibit accelerated mucosal regeneration during acute colitis. Mechanistically, macrophage-derived VISTA interacts with leucine-rich repeats and immunoglobulin-like domain 1 (LRIG1) in intestinal stem cells and suppresses peroxisome proliferator-activated receptor alpha (PPARα), leading to impeded growth of intestinal organoids and increased epithelial damage in mice with DSS-induced colitis. These findings reveal a pathogenic function of macrophage-derived VISTA in epithelial damage during colitis. Targeting the VISTA/LRIG1 axis could promote epithelial repair and serve as a promising therapeutic strategy for patients with IBD.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944751","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

Functional importance of bile acid-FXR signaling in neonatal immunity and disease 胆汁酸- fxr信号在新生儿免疫和疾病中的功能重要性。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-29 DOI: 10.1038/s41423-025-01337-z

Douglas G. Burrin, Greg Guthrie, Caitlin Vonderohe

引用次数: 0

Engineering TCR-preserved allogeneic CAR-T cells: leveraging cancer immune evasion principles to establish T-cell tolerance. 工程tcr保存的异体CAR-T细胞：利用癌症免疫逃避原理建立t细胞耐受性。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-26 DOI: 10.1038/s41423-025-01341-3

Xiaodong Zheng, Zhigang Tian

引用次数: 0

Author Correction: SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors 作者更正：SMAD7在CAR-T细胞中的表达提高了实体瘤的持久性和安全性。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-26 DOI: 10.1038/s41423-025-01330-6

Sixin Liang, Rui Zheng, Baile Zuo, Jia Li, Yiyi Wang, Yujie Han, Hao Dong, Xiaojuan Zhao, Yiting Zhang, Pengju Wang, Ruotong Meng, Lintao Jia, Angang Yang, Bo Yan

引用次数: 0

SARDH in the 1-C metabolism sculpts the T-cell fate and serves as a potential cancer therapeutic target. 1-C代谢中的SARDH塑造了t细胞的命运，并作为潜在的癌症治疗靶点。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-08-20 DOI: 10.1038/s41423-025-01331-5

Wen Si, Sijin Cheng, Haiyin He, Yu Zhang, Yuhui Miao, Dingcheng Yi, Mengjiao Ni, Anqiang Wang, Hongtao Fan, Yufei Bo, Chang Liu, Zhaode Bu, Linnan Zhu, Zemin Zhang

{"title":"SARDH in the 1-C metabolism sculpts the T-cell fate and serves as a potential cancer therapeutic target.","authors":"Wen Si, Sijin Cheng, Haiyin He, Yu Zhang, Yuhui Miao, Dingcheng Yi, Mengjiao Ni, Anqiang Wang, Hongtao Fan, Yufei Bo, Chang Liu, Zhaode Bu, Linnan Zhu, Zemin Zhang","doi":"10.1038/s41423-025-01331-5","DOIUrl":"10.1038/s41423-025-01331-5","url":null,"abstract":"T-cell metabolism plays a pivotal role in defining T-cell functional states. Through analysis of a comprehensive pancancer single-cell transcriptional atlas, we identified SARDH, an enzyme involved in one-carbon (1-C) metabolism, as a potential T-cell metabolic checkpoint. SARDH significantly impacts T-cell fate and function, leading to impaired tumor control efficacy. Knocking down SARDH resulted in sarcosine accumulation and reduced consumption of S-adenosylmethionine (SAM), a critical methyl donor for epigenetic modulation, likely due to the shift in glycine-to-sarcosine homeostasis. Deletion of SARDH increased H3K79me2 modification at NF-κB-activating genes, thereby augmenting NF-κB signaling and T-cell function. Additionally, we observed transcriptional dysregulation of 1-C metabolism within tumors across various cancer types, which was often accompanied by increased sarcosine levels. Sarcosine was found to induce SARDH upregulation, suggesting a feedback mechanism for metabolic homeostasis in T cells within tumors. These findings underscore the potential effects and mechanism of targeting 1-C metabolism, particularly SARDH, as an avenue for cancer therapy.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882313","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

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":" ","pages":""},"PeriodicalIF":19.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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