Cellular &Molecular Immunology最新文献_第3页

Antisense to human CD39 dysregulates immune metabolism in inflammatory bowel disease. 人CD39的反义蛋白在炎症性肠病中调节免疫代谢失调。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-26 DOI: 10.1038/s41423-025-01295-6

Lina Zhang, Cortney Cagle, Du Hanh Nguyen, Graziela Scheuer Gomes, Barbora Gromova, Eva Csizmadia, Arian Karimitar, Ghee Rye Lee, Guanqing Chen, Efi Kokkotou, Laurie Grossberg, Sizun Jiang, Adam S Cheifetz, Satya K Kota, Maria Serena Longhi

{"title":"Antisense to human CD39 dysregulates immune metabolism in inflammatory bowel disease.","authors":"Lina Zhang, Cortney Cagle, Du Hanh Nguyen, Graziela Scheuer Gomes, Barbora Gromova, Eva Csizmadia, Arian Karimitar, Ghee Rye Lee, Guanqing Chen, Efi Kokkotou, Laurie Grossberg, Sizun Jiang, Adam S Cheifetz, Satya K Kota, Maria Serena Longhi","doi":"10.1038/s41423-025-01295-6","DOIUrl":"10.1038/s41423-025-01295-6","url":null,"abstract":"Defective CD39 levels contribute to an imbalance between Tregs and Th17 effectors in inflammatory bowel disease (IBD). CD39 initiates an ATP hydrolysis cascade that culminates with the generation of adenosine, an immune metabolite that is key to tissue homeostasis. Human CD39 is regulated by an endogenous antisense RNA (CD39-AS) that is markedly elevated in IBD Tregs and Th17 cells. In this study, we investigated how CD39-AS affects the function of Tregs and Th17 cells in healthy subjects and IBD patients. We report that CD39-AS RNA is present in two main splice variants that are specifically expressed by Tregs or Th17 cells. Blockade of CD39-AS via self-delivering oligonucleotides targeting the splice variant expressed in Tregs results in a decrease of glucose transport and glycolysis and in enhanced Treg function and stability in IBD. In Th17 cells, silencing of CD39-AS limits oxidative responses and ameliorates mitochondrial health. These metabolic effects are also noted in a model of experimental colitis in humanized mice, along with reduced disease activity. Thus, in vivo administration of oligonucleotides targeting the Treg or Th17 cell CD39-AS variant limits disease activity, decreases the expression of GLUT1 and improves mitochondrial health in gut-derived CD4 lymphocytes. Mechanistically, activation of HIF-1α and STAT3 results in the upregulation of CD39-AS in IBD cells. In conclusion, CD39-AS is an important modulator of Treg and Th17 cell metabolism. Interference with this antisense RNA, or the factors favoring its upregulation, might contain inflammation and halt disease progression in IBD by restoring immune metabolism and Treg functional stability.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141552","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

Adjusting the scope of natural killer cells in cancer therapy. 调整自然杀伤细胞在癌症治疗中的作用范围。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-23 DOI: 10.1038/s41423-025-01297-4

Zihen Shen, Xiangpeng Meng, Jai Rautela, Michael Chopin, Nicholas D Huntington

引用次数: 0

Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease. 酒精相关性肝病的免疫机制和新出现的治疗靶点

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-21 DOI: 10.1038/s41423-025-01291-w

Haiyuan Shen, Suthat Liangpunsakul, Yasuko Iwakiri, Gyongyi Szabo, Hua Wang

引用次数: 0

Targeting Lp-PLA2 inhibits profibrotic monocyte-derived macrophages in silicosis through restoring cardiolipin-mediated mitophagy. 靶向Lp-PLA2通过恢复心磷脂介导的线粒体自噬抑制矽肺中纤维化单核细胞来源的巨噬细胞。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-19 DOI: 10.1038/s41423-025-01288-5

Shifeng Li, Hong Xu, Shupeng Liu, Jinkun Hou, Yueyin Han, Chen Li, Yupeng Li, Gaigai Zheng, Zhongqiu Wei, Fang Yang, Shuwei Gao, Shiyao Wang, Jing Geng, Huaping Dai, Chen Wang

{"title":"Targeting Lp-PLA2 inhibits profibrotic monocyte-derived macrophages in silicosis through restoring cardiolipin-mediated mitophagy.","authors":"Shifeng Li, Hong Xu, Shupeng Liu, Jinkun Hou, Yueyin Han, Chen Li, Yupeng Li, Gaigai Zheng, Zhongqiu Wei, Fang Yang, Shuwei Gao, Shiyao Wang, Jing Geng, Huaping Dai, Chen Wang","doi":"10.1038/s41423-025-01288-5","DOIUrl":"https://doi.org/10.1038/s41423-025-01288-5","url":null,"abstract":"Monocyte-derived macrophages (MoMacs) are the most important effector cells that cause pulmonary fibrosis. However, the characteristics of MoMac differentiation in silicosis and the mechanisms by which MoMacs affect the progression of pulmonary fibrosis remain unclear. Integration of single-cell and spatial transcriptomic analyses revealed that the silicosis niche was occupied by a subset of MoMacs, identified as Spp1hiMacs, which remain in an immature transitional state of differentiation during silicosis. This study investigated the mechanistic foundations of mitochondrial damage induced by the lipoprotein-associated phospholipase A2 (Lp-PLA2, encoded by Pla2g7)-acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1)-cardiolipin (CL) signaling pathway, which interferes with Spp1hiMac differentiation. We demonstrated that in SiO2-induced MoMacs, Lp-PLA2 induces abnormal CL acylation through the activation of ALCAT1, resulting in impaired mitochondrial localization of PINK1 and LC3B and mitochondrial autophagy defects. Simultaneously, lysosomal dysfunction causes the release of the lysosomal protein cathepsin B into the cytoplasm, which involves M1 and M2 macrophage polarization and the activation of proinflammatory and profibrotic pathways. Furthermore, we assessed the efficacy of the Lp-PLA2 inhibitor darapladib in ameliorating silica-induced pulmonary fibrosis in a murine model. Our findings enhance our understanding of silicosis pathogenesis and offer promising opportunities for developing targeted therapies to mitigate fibrotic progression and maintain lung function in affected individuals.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101429","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

Synergistic effects of LCN2 and TWEAK on the progression of psoriasis. LCN2和TWEAK对银屑病进展的协同作用。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-15 DOI: 10.1038/s41423-025-01292-9

Kaixuan Ren, Xueting Peng, Xudong Duan, Rongfang Feng, Christopher Cook, Mei Lu, Min Li, Hanjiang Gu, Xiaoyu Wang, Guorong Deng, Huiqun Ma, Yale Liu, Yumin Xia

{"title":"Synergistic effects of LCN2 and TWEAK on the progression of psoriasis.","authors":"Kaixuan Ren, Xueting Peng, Xudong Duan, Rongfang Feng, Christopher Cook, Mei Lu, Min Li, Hanjiang Gu, Xiaoyu Wang, Guorong Deng, Huiqun Ma, Yale Liu, Yumin Xia","doi":"10.1038/s41423-025-01292-9","DOIUrl":"https://doi.org/10.1038/s41423-025-01292-9","url":null,"abstract":"Lipocalin 2 (LCN2) and the TWEAK/Fn14 signaling pathways are pivotal in psoriasis, influencing epidermal development, inflammatory cell chemotaxis, and inflammatory factor release. Despite their significant roles, the intricate relationship between LCN2 and TWEAK/Fn14 pathways remains unclear. Our study revealed the correlation between the expression of TWEAK, LCN2, and Fn14 in psoriatic lesions. We found that TWEAK is expressed by keratinocytes and macrophages, while LCN2 is expressed by keratinocytes and neutrophils. Surface plasmon resonance experiments demonstrated binding between LCN2 and Fn14, which was further validated by co-immunoprecipitation and cellular co-localization via immunofluorescence. In vitro, LCN2 promoted macrophage differentiation and TWEAK secretion, enhanced TWEAK and Fn14 expression in keratinocytes, and activated the MAPK signaling pathway. TWEAK upregulated LCN2 expression in neutrophils but not in keratinocytes. Bulk RNA-seq analysis revealed a synergistic effect of LCN2 and TWEAK in promoting inflammatory cytokine expression in keratinocytes, with enhanced MAPK pathway activation in the presence of M5 cytokines. Lcn2 knockout reduced Fn14 expression in skin lesions and serum TWEAK levels of imiquimod-induced murine psoriasis model, while Fn14 knockout attenuated the epidermal hyperplasia-promoting effects of TWEAK and LCN2. Overexpression of Fn14 in keratinocytes led to higher TWEAK expression upon LCN2 stimulation, suggesting a self-reinforcing loop among TWEAK, LCN2, and Fn14. We propose that LCN2 synergizes with TWEAK through Fn14 to drive psoriasis pathogenesis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076321","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

Sexual dimorphism of lung immune-regulatory units imprint biased pulmonary fibrosis. 肺免疫调节单位的性别二态性印记偏倚性肺纤维化。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-14 DOI: 10.1038/s41423-025-01293-8

Peng Xiang, Liwen Wang, Xu Feng, Qi Guo, Genqing Xie, Langqing Sheng, Linyun Chen, Jianhui Teng, Jinlin Yang, Xuecheng Wu, Xi Peng, Renbin Lu, Xianghang Luo, Jie Wen, Hai-Yan Zhou

{"title":"Sexual dimorphism of lung immune-regulatory units imprint biased pulmonary fibrosis.","authors":"Peng Xiang, Liwen Wang, Xu Feng, Qi Guo, Genqing Xie, Langqing Sheng, Linyun Chen, Jianhui Teng, Jinlin Yang, Xuecheng Wu, Xi Peng, Renbin Lu, Xianghang Luo, Jie Wen, Hai-Yan Zhou","doi":"10.1038/s41423-025-01293-8","DOIUrl":"https://doi.org/10.1038/s41423-025-01293-8","url":null,"abstract":"Pulmonary fibrosis (PF) is sexually dimorphic, with a relatively high prevalence and severity in males; however, the mechanism remains unclear. Our study revealed pronounced sexual dimorphism of immune cell genes in the lung, among which grancalcin (GCA) showed profound sex differences. GCA was produced by lung-infiltrating bone marrow macrophages triggered by heightened inflammation in the lung. However, a unique HTR2C+ alveolar macrophage population enriched in female lungs metabolically reprogramed bone marrow-derived macrophages and constrained local GCA amplification. As a novel chemokine, GCA bound to protein tyrosine phosphatase receptor type T (PTPRT) in Th17 cells and facilitated pathogenic lung infiltration by activating the ROCK1-MLC pathway, thus aggravating lung fibrosis. Notably, both GCA and Th17 cells abundantly accumulated in lung biopsies from male PF patients but not in those from female patients. GCA-neutralizing antibodies in combination with pirfenidone, a prescribed medication for treating fibrosis, provided superior effectiveness and survival rates against PF compared with treatment with pirfenidone alone. Overall, our findings reveal that sex-biased lung fibrosis is shaped by lung immune-regulatory units, which could be targeted to limit lung fibrosis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":""},"PeriodicalIF":21.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983072","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

Systematic mining and quantification reveal the dominant contribution of non-HLA variations to acute graft-versus-host disease. 系统的挖掘和量化揭示了非hla变异对急性移植物抗宿主病的主要贡献。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-01 Epub Date: 2025-03-04 DOI: 10.1038/s41423-025-01273-y

Shuang Liang, Yu-Jian Kang, Mingrui Huo, De-Chang Yang, Min Ling, Keli Yue, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Chen-Rui Xia, Jing-Yi Li, Ning Wu, Ruoyang Liu, Xinyu Dong, Jiangying Liu, Ge Gao, Xiao-Jun Huang

{"title":"Systematic mining and quantification reveal the dominant contribution of non-HLA variations to acute graft-versus-host disease.","authors":"Shuang Liang, Yu-Jian Kang, Mingrui Huo, De-Chang Yang, Min Ling, Keli Yue, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Chen-Rui Xia, Jing-Yi Li, Ning Wu, Ruoyang Liu, Xinyu Dong, Jiangying Liu, Ge Gao, Xiao-Jun Huang","doi":"10.1038/s41423-025-01273-y","DOIUrl":"10.1038/s41423-025-01273-y","url":null,"abstract":"Human leukocyte antigen (HLA) disparity between donors and recipients is a key determinant triggering intense alloreactivity, leading to a lethal complication, namely, acute graft-versus-host disease (aGVHD), after allogeneic transplantation. Moreover, aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation. Protocols for HLA-haploidentical hematopoietic cell transplantation (haploHCT) have been established successfully and widely applied, further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD. On the basis of our time-consecutive large haploHCT cohort (with a homogenous discovery set and an extended confirmatory set), we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors. In addition to identifying multiple loss-of-function (LoF) risk variations in non-HLA coding genes, our data-driven study revealed that non-HLA genetic variations, independent of HLA disparity, contributed the most to the occurrence of aGVHD. This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT. Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells. Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":"501-511"},"PeriodicalIF":21.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540287","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

"Electric power boost" for CAR-T-cell potency. car - t细胞效能的“电力提升”。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-01 Epub Date: 2025-03-21 DOI: 10.1038/s41423-025-01279-6

Yadan Bai, Wanlu Liu, Lie Wang, Linrong Lu

引用次数: 0

Comment on: Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation. 糖原合成酶激酶3通过调节NFAT激活来控制t细胞衰竭。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-01 Epub Date: 2025-04-02 DOI: 10.1038/s41423-025-01277-8

Bastien Moës, Christopher E Rudd

引用次数: 0

Lipid droplets restrict phagosome formation in antifungal immunity. 脂滴抑制抗真菌免疫中吞噬体的形成。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s41423-025-01282-x

Wanwei Sun, Han Wu, Guimin Zhao, Qing Shui, Lei Zhang, Xiaoxi Luan, Tian Chen, Feng Liu, Yi Zheng, Wei Zhao, Xiaopeng Qi, Bingyu Liu, Chengjiang Gao

{"title":"Lipid droplets restrict phagosome formation in antifungal immunity.","authors":"Wanwei Sun, Han Wu, Guimin Zhao, Qing Shui, Lei Zhang, Xiaoxi Luan, Tian Chen, Feng Liu, Yi Zheng, Wei Zhao, Xiaopeng Qi, Bingyu Liu, Chengjiang Gao","doi":"10.1038/s41423-025-01282-x","DOIUrl":"10.1038/s41423-025-01282-x","url":null,"abstract":"Lipid droplets (LDs) are intracellular organelles that can be induced and interact with phagosomes during the process of pathogen phagocytosis in macrophages. However, the function of LDs in phagocytosis remains elusive. Here, we unveil the role of LDs in modulating phagosome formation via a fungal infection model. Specifically, LD accumulation restricted the degree of phagosome formation and protected macrophages from death. Mechanistically, LD formation competitively consumed the intracellular endoplasmic reticulum membrane and altered RAC1 translocation and GTPase activity, which resulted in limited phagosome formation in macrophages during fungal engulfment. Mice with Hilpda-deficient macrophages were more susceptible to the lethal sequelae of systemic infection with C. albicans. Notably, administration of the ATGL inhibitor atglistatin improved host outcomes in disseminated fungal infections. Taken together, our study elucidates the mechanism by which LDs control phagosome formation to prevent immune cell death and offers a potential drug target for the treatment of C. albicans infections.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":" ","pages":"468-484"},"PeriodicalIF":21.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802591","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