Cellular &Molecular Immunology最新文献_第6页

Immunopathogenic mechanisms and immunoregulatory therapies in MASLD MASLD的免疫致病机制和免疫调节治疗。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-06-10 DOI: 10.1038/s41423-025-01307-5

Yong He, Yingfen Chen, Shengying Qian, Schalk van Der Merwe, Debanjan Dhar, David A. Brenner, Frank Tacke

{"title":"Immunopathogenic mechanisms and immunoregulatory therapies in MASLD","authors":"Yong He, Yingfen Chen, Shengying Qian, Schalk van Der Merwe, Debanjan Dhar, David A. Brenner, Frank Tacke","doi":"10.1038/s41423-025-01307-5","DOIUrl":"10.1038/s41423-025-01307-5","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver disease worldwide, with an estimated global prevalence of approximately 30%; however, effective pharmacotherapies are still limited due to its complex pathogenesis and etiology. Therefore, a more thorough understanding of disease pathogenesis is urgently needed. An increasing number of studies suggest that MASLD and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are driven by chronic overnutrition, multiple genetic susceptibility factors, and pathogenic consequences, including hepatocyte damage and liver inflammation. Hepatic inflammation is the key event fueling the conversion from simple steatosis to steatohepatitis and fibrosis. Current therapies for MASH, including the recently approved thyroid hormone receptor-beta agonist resmetirom or the available incretin mimetics, mainly target metabolic injury to the liver but not inflammation directly. In this review, we provide an in-depth discussion of current data related to the immunological mechanisms of MASLD and summarize the effects of current and experimental therapies on immunoregulation in MASLD.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 10","pages":"1159-1177"},"PeriodicalIF":19.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-025-01307-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265385","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

Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond 从天然受体到合成受体的转变：扩展t细胞工程及其他。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-06-06 DOI: 10.1038/s41423-025-01304-8

Li Yu, Yue Liu, Xin Lin

{"title":"Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond","authors":"Li Yu, Yue Liu, Xin Lin","doi":"10.1038/s41423-025-01304-8","DOIUrl":"10.1038/s41423-025-01304-8","url":null,"abstract":"T-cell immunotherapy has progressed rapidly, evolving from native T-cell receptor biology to the development of innovative synthetic receptors that extend therapeutic applications beyond cancer. This review explores engineering strategies, ranging from natural TCRs to synthetic receptors, that increase T-cell activation and therapeutic potential. We begin by highlighting the foundational role of native receptors in the T-cell response, emphasizing how these structural and functional insights inform the design of next-generation synthetic receptors. Comparisons between CAR and TCR-like synthetic receptors underscore their respective advantages in specificity, efficacy, and safety, as well as potential areas for further improvement. In addition, gene editing technologies such as CRISPR-Cas9 enable precise modifications to the T-cell genome, enhancing receptor performance and minimizing immunogenic risks. In addition to tumors, these engineered T cells can be directed against viral infections, autoimmune disorders, and other diseases. We also explore advanced strategies that engage multiple immune cell types to achieve synergistic, durable responses. By demonstrating how native and synthetic receptors collectively drive innovation, this review aims to inspire new research directions and ultimately expand the scope of T-cell engineering for universal therapeutic applications.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 7","pages":"712-729"},"PeriodicalIF":19.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246716","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

CCR2+ monocytes promote memory CD8+ T-cell differentiation via membrane-bound TGF-β CCR2+单核细胞通过膜结合TGF-β促进记忆性CD8+ t细胞分化。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-06-03 DOI: 10.1038/s41423-025-01299-2

Lina Sun, Cangang Zhang, Anjun Jiao, Yanhong Su, Tianzhe Zhang, Qianhao Wang, Yao Ge, Chen Yang, Ning Yuan, Lianjun Zhang, Chenming Sun, Liang Chen, Lilin Ye, Baojun Zhang

{"title":"CCR2+ monocytes promote memory CD8+ T-cell differentiation via membrane-bound TGF-β","authors":"Lina Sun, Cangang Zhang, Anjun Jiao, Yanhong Su, Tianzhe Zhang, Qianhao Wang, Yao Ge, Chen Yang, Ning Yuan, Lianjun Zhang, Chenming Sun, Liang Chen, Lilin Ye, Baojun Zhang","doi":"10.1038/s41423-025-01299-2","DOIUrl":"10.1038/s41423-025-01299-2","url":null,"abstract":"Upon antigen recognition, CD8+ T cells undergo robust expansion and differentiation to give rise to effector and memory CD8+ T cells. The spatial determinants of the fate of effector and memory CD8+ T cells during acute infection are poorly understood. By integrating single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics, we revealed that naïve CD8+ T cells adopted a divergent trajectory in which they rapidly differentiated into memory precursor (MP) cells and IFN-responsive cells, with the latter representing the entry point of the effector T-cell lineage. In the spleen, monocytes largely colocalized with CD8+ MP cells following antigen stimulation. Specifically, compared with dendritic cells (DCs), the Ly6ChiCCR2+ subset of monocytes promotes memory CD8+ T-cell differentiation. Mechanistically, monocytes express high levels of membrane-bound transforming growth factor-β (TGF-β), which is activated by thrombospondin-1 (TSP-1) to drive the memory CD8+ T-cell program through Smad signaling. Overall, our study reveals a novel spatial mechanism for CD8+ T-cell fate decisions, shedding light on the importance of monocytes in fostering memory CD8+ T-cell development in a cell‒cell contact- and TGF-β-dependent manner.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 8","pages":"869-888"},"PeriodicalIF":19.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215090","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

Liver macrophages: development, dynamics, and functions 肝巨噬细胞：发育、动态和功能。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-06-03 DOI: 10.1038/s41423-025-01298-3

Ysbrand Nusse, Paul Kubes

{"title":"Liver macrophages: development, dynamics, and functions","authors":"Ysbrand Nusse, Paul Kubes","doi":"10.1038/s41423-025-01298-3","DOIUrl":"10.1038/s41423-025-01298-3","url":null,"abstract":"The liver is a sizeable visceral organ whose primary functions involve nutrient metabolism, clearance of toxins, and energy storage. Besides these critical functions, the liver is also a major immunological site. It is populated by several specialized resident immune cells, including B cells, T Cells, dendritic cells, and several populations of macrophages. It is also the site for the production and release of acute-phase proteins during inflammation. One reason for garrisoning these immune sentinels and effectors in the liver is its relative location in the circulatory system. The liver is the first significant organ downstream of the intestine, where blood originating from the intestine enters the liver through the portal vein. This organization facilitates the liver’s uptake and processing of nutrient-rich blood directly from the intestinal source. However, the intestine is also home to trillions of microbes, many of which are commensals but also represent potential pathogens. As such, the portal blood supply represents an avenue for systemic infection. To sterilize the portal blood, the liver immune system filters pathogens, which is primarily accomplished by liver macrophages. Here, we will discuss the major populations of macrophages resident in the liver, their location, functions, development, and role in maintaining the liver in the face of injury and infection.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 10","pages":"1178-1189"},"PeriodicalIF":19.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41423-025-01298-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215091","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

γδ+ T-cell-derived IL-17A stimulates airway epithelial/stromal cells to secrete G-CSF, promoting lung-specific pathogenic Siglec-F+ neutrophil development in PPE-induced emphysema γδ+ t细胞源性IL-17A刺激气道上皮/间质细胞分泌G-CSF，促进肺特异性致病性siglece - f +中性粒细胞在肺气肿中的发育。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-06-03 DOI: 10.1038/s41423-025-01301-x

JungHyub Hong, Myeong-Ho Kang, Jinjoo Lee, Min-Suk Cha, Yoe-Sik Bae, Hye Young Kim, Yong Taik Lim, Yong-Soo Bae

{"title":"γδ+ T-cell-derived IL-17A stimulates airway epithelial/stromal cells to secrete G-CSF, promoting lung-specific pathogenic Siglec-F+ neutrophil development in PPE-induced emphysema","authors":"JungHyub Hong, Myeong-Ho Kang, Jinjoo Lee, Min-Suk Cha, Yoe-Sik Bae, Hye Young Kim, Yong Taik Lim, Yong-Soo Bae","doi":"10.1038/s41423-025-01301-x","DOIUrl":"10.1038/s41423-025-01301-x","url":null,"abstract":"Neutrophils play a pivotal role in the progression of IL-17-mediated airway inflammation, but the mechanisms underlying their pathological differentiation remain poorly understood. In this study, we identified a distinct population of lung-specific pathogenic Siglec-F+ neutrophils in a porcine pancreatic elastase (PPE)-induced mouse model of emphysema. Compared with conventional neutrophils, these Siglec-F+ neutrophils exhibited increased phagocytic activity, increased extracellular trap formation, increased production of proinflammatory cytokines, and reduced IL-10 levels. During the early phase of acute inflammation following PPE instillation, IL-17A levels in the lungs increase, which is driven primarily by γδ+ T cells. IL-17A stimulated lung epithelial/stromal cells to secrete granulocyte colony-stimulating factor (G-CSF), which promoted the differentiation of Siglec-F+ neutrophils via the JAK2/STAT3 pathway and the PI3K-independent mTOR and p38 MAPK signaling pathways. Neutralizing G-CSF or inhibiting JAK2/STAT3, mTOR or p38 MAPK signaling significantly suppressed Siglec-F+ neutrophil development, resulting in the alleviation of emphysematous symptoms. Our findings underscore the crucial role of Siglec-F+ neutrophils in the pathogenesis of PPE-induced emphysema and suggest that targeting the IL-17A/G-CSF axis or G-CSF receptor downstream signaling pathways may represent a promising therapeutic strategy for treating emphysema.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"22 7","pages":"791-805"},"PeriodicalIF":19.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215092","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

Cholinergic B cells: New players in immune regulation and tissue homeostasis 胆碱能B细胞：免疫调节和组织稳态的新参与者。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-30 DOI: 10.1038/s41423-025-01300-y

Fan Xiao, Lam Ng, Kongyang Ma, Chong Deng, Xiaoxia Zhu, Hejian Zou, Haijing Wu, Liwei Lu

引用次数: 0

Cytotoxic T cells meet complement: granzyme K as a new initiator of inflammation 细胞毒性T细胞遇到补体：颗粒酶K作为炎症的新启动器。

IF 19.8 1区医学

Cellular &Molecular Immunology Pub Date : 2025-05-29 DOI: 10.1038/s41423-025-01303-9

Junyi Zhao, Xing Guo, Wanli Liu, Conglei Li

引用次数: 0

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 19.8 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":"22 7","pages":"730-742"},"PeriodicalIF":19.8,"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 19.8 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 19.8 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