Experimental and Molecular Medicine最新文献

{"title":"The MCP-3/Ccr3 axis contributes to increased bone mass by affecting osteoblast and osteoclast differentiation.","authors":"Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Xiangguo Che, Je-Yong Choi, Jeong-Tae Koh, Nacksung Kim","doi":"10.1038/s12276-024-01344-6","DOIUrl":"https://doi.org/10.1038/s12276-024-01344-6","url":null,"abstract":"<p><p>Several CC subfamily chemokines have been reported to regulate bone metabolism by affecting osteoblast or osteoclast differentiation. However, the role of monocyte chemotactic protein 3 (MCP-3), a CC chemokine, in bone remodeling is not well understood. Here, we show that MCP-3 regulates bone remodeling by promoting osteoblast differentiation and inhibiting osteoclast differentiation. In a Ccr3-dependent manner, MCP-3 promoted osteoblast differentiation by stimulating p38 phosphorylation and suppressed osteoclast differentiation by upregulating interferon beta. MCP-3 increased bone morphogenetic protein 2-induced ectopic bone formation, and mice with MCP-3-overexpressing osteoblast precursor cells presented increased bone mass. Moreover, MCP-3 exhibited therapeutic effects by abrogating receptor activator of nuclear factor kappa-B ligand-induced bone loss. Therefore, MCP-3 has therapeutic potential for diseases involving bone loss due to its positive role in osteoblast differentiation and negative role in osteoclast differentiation.</p>","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic analysis reveals dynamic activation of cellular signaling pathways regulating beige adipogenesis","authors":"Dong Soo Kyung,&nbsp;Eunmin Lee,&nbsp;Sehyun Chae,&nbsp;Yeonho Son,&nbsp;Ye-Jin Moon,&nbsp;Daehee Hwang,&nbsp;Jong Kyoung Kim,&nbsp;Yun-Hee Lee,&nbsp;Je Kyung Seong","doi":"10.1038/s12276-024-01252-9","DOIUrl":"10.1038/s12276-024-01252-9","url":null,"abstract":"PDGFRA+ cells have been identified as adipocyte stem cells (ASCs) that differentiate into beige adipocytes in white adipose tissue (WAT) following thermogenic stimuli. To elucidate the molecular heterogeneity of ASCs, we conducted single-cell transcriptomic profiling of PDGFRA+ cells isolated from the inguinal WAT (iWAT) of mice treated with the beta3 adrenergic receptor agonist CL316243. Single-cell RNA-seq revealed nine major clusters, which were categorized into four groups: resting, proliferating, differentiating, and adipogenic factor-expressing cells (AFECs). Trajectory analysis revealed sequential activation of molecular pathways, including the Hedgehog and Notch signaling pathways, during beige adipogenesis. AFECs expressed Dpp4 and did not differentiate into adipocytes in culture or after transplantation. Furthermore, genetic lineage tracing studies indicated that DPP4+ cells did not differentiate into adipocytes in iWAT during CL316243-induced beige adipogenesis. However, high-fat diet feeding led to the recruitment of adipocytes from DPP4+ cells in iWAT. Overall, this study improved our understanding of the dynamic molecular basis of beige adipogenesis and the potential contribution of DPP4+ adipocyte lineages to the pathological expansion of WAT during diet-induced obesity. This research examines beige adipogenesis, or the creation of ‘beige’ fat cells that burn energy and could help fight obesity. The scientists discovered a group of cells, identifed by specific markers PDGFRA and DPP4, which serve as a source for beige adipogenesis but don’t turn into beige fat cells themselves. They also found that these cells can change to become fat cells under certain situations, like a high-fat diet. The study also showed that the Hedgehog and Notch signaling pathways are vital in the transformation of PDGFRA+ cells into beige fat cells. These discoveries could be important for developing anti-obesity therapeutics. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01252-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","authors":"Jung-Hwan Baek,&nbsp;Myung Sup Kim,&nbsp;Hye Ryeon Jung,&nbsp;Min-Seon Hwang,&nbsp;Chan-ho Lee,&nbsp;Dai Hoon Han,&nbsp;Yong-ho Lee,&nbsp;Eugene C. Yi,&nbsp;Seung-Soon Im,&nbsp;Ilseon Hwang,&nbsp;Kyungeun Kim,&nbsp;Joon-Yong Chung,&nbsp;Kyung-Hee Chun","doi":"10.1038/s12276-024-01343-7","DOIUrl":"10.1038/s12276-024-01343-7","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01343-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: NOTCH localizes to mitochondria through the TBC1D15-FIS1 interaction and is stabilized via blockade of E3 ligase and CDK8 recruitment to reprogram tumor-initiating cells","authors":"Hye Yeon Choi,&nbsp;Yicheng Zhu,&nbsp;Xuyao Zhao,&nbsp;Simran Mehta,&nbsp;Juan Carlos Hernandez,&nbsp;Jae-Jin Lee,&nbsp;Yi Kou,&nbsp;Risa Machida,&nbsp;Mauro Giacca,&nbsp;Giannino Del Sal,&nbsp;Ratna Ray,&nbsp;Hyungjin Eoh,&nbsp;Stanley M. Tahara,&nbsp;Lin Chen,&nbsp;Hidekazu Tsukamoto,&nbsp;Keigo Machida","doi":"10.1038/s12276-024-01325-9","DOIUrl":"10.1038/s12276-024-01325-9","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01325-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone lysine methylation modifiers controlled by protein stability","authors":"Sungryul Park,&nbsp;Jin Hwa Cho,&nbsp;Jeong-Hoon Kim,&nbsp;Jung-Ae Kim","doi":"10.1038/s12276-024-01329-5","DOIUrl":"10.1038/s12276-024-01329-5","url":null,"abstract":"Histone lysine methylation is pivotal in shaping the epigenetic landscape and is linked to cell physiology. Coordination of the activities of multiple histone lysine methylation modifiers, namely, methyltransferases and demethylases, modulates chromatin structure and dynamically alters the epigenetic landscape, orchestrating almost all DNA-templated processes, such as transcription, DNA replication, and DNA repair. The stability of modifier proteins, which is regulated by protein degradation, is crucial for their activity. Here, we review the current knowledge of modifier-protein degradation via specific pathways and its subsequent impact on cell physiology through epigenetic changes. By summarizing the functional links between the aberrant stability of modifier proteins and human diseases and highlighting efforts to target protein stability for therapeutic purposes, we aim to promote interest in defining novel pathways that regulate the degradation of modifiers and ultimately increase the potential for the development of novel therapeutic strategies. Histone modifications, such as methylation, are key in controlling gene expression by changing the structure of chromatin, the DNA and protein mix in our cells’ nucleus. This study investigates how the stability of histone lysine methylation modifiers—enzymes that add or remove methyl groups from histones—is managed. It’s a study aimed at understanding the delicate balance of these modifiers in the cell. The researchers studied various cell processes, including the ubiquitin-proteasome system, and post-translational modifications, that affect the stability of these enzymes. The results show changing the stability of these modifiers can alter histone methylation patterns, suggesting new ways to target diseases like cancer. Researchers conclude that understanding the control of enzyme stability offers a promising path for developing therapies that can correct abnormal gene expression by targeting the enzymes responsible for histone modifications. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01329-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach","authors":"Soie Kwon,&nbsp;Seongmin Cheon,&nbsp;Kyu-Hong Kim,&nbsp;Areum Seo,&nbsp;Eunjin Bae,&nbsp;Jae Wook Lee,&nbsp;Ran-Hui Cha,&nbsp;Jin Ho Hwang,&nbsp;Yong Chul Kim,&nbsp;Dong Ki Kim,&nbsp;Yon Su Kim,&nbsp;Dohyun Han,&nbsp;Seung-Hee Yang","doi":"10.1038/s12276-024-01319-7","DOIUrl":"10.1038/s12276-024-01319-7","url":null,"abstract":"Chronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epithelial cells and kidney tissue from a 5/6 nephrectomy rat model. Multidisciplinary analysis across kidney fibrosis models revealed 351 differentially expressed proteins associated with kidney fibrosis, and they were enriched in processes related to the extracellular matrix, kidney aging, and mitochondrial functions. Network analysis of the selected proteins revealed five crucial proteins, of which transgelin emerged as a candidate protein that interacts with known fibrosis-related proteins. Concordantly, the gene expression of transgelin in the kidney tissue from the 5/6 nephrectomy model was elevated. Transgelin expression in kidney tissue gradually increased from intermediate to advanced fibrosis stages in 5/6 Nx rats and mice with unilateral ureteral obstruction. Subsequent validation in kidney tissue and urine samples from patients with CKD confirmed the upregulation of transgelin, particularly under advanced disease stages. Moreover, we investigated whether blocking TAGLN ameliorated kidney fibrosis and reduced reactive oxygen species levels in cellular models. In conclusion, our proteomic approach identified TAGLN as a potential noninvasive biomarker and therapeutic target for CKD-associated kidney fibrosis, suggesting its role in modulating mitochondrial dysfunction and oxidative stress responses. Chronic kidney disease is caused by kidney fibrosis, where healthy kidney tissue becomes scar, affecting kidney function. This research aimed to find noninvasive signs of kidney fibrosis by studying proteins in human kidney cells and animal CKD models. They used mass spectrometry, a method to identify and quantify proteins, to find potential signs in the body fluids that could show kidney fibrosis without needing kidney biopsy. The study found that the protein TAGLN increases in kidney tissue and urine in CKD conditions, suggesting it could be a useful sign of kidney fibrosis. Further tests showed that blocking TAGLN could reduce kidney fibrosis, indicating its potential as a target for new treatments. The researchers conclude that TAGLN is a promising sign of kidney fibrosis and could lead to better diagnostic and treatment options for CKD patients. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01319-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrative single-cell atlas for exploring the cellular and temporal specificity of genes related to neurological disorders during human brain development","authors":"Seoyeon Kim,&nbsp;Jihae Lee,&nbsp;In Gyeong Koh,&nbsp;Jungeun Ji,&nbsp;Hyun Jung Kim,&nbsp;Eunha Kim,&nbsp;Jihwan Park,&nbsp;Jong-Eun Park,&nbsp;Joon-Yong An","doi":"10.1038/s12276-024-01328-6","DOIUrl":"10.1038/s12276-024-01328-6","url":null,"abstract":"Single-cell technologies have enhanced comprehensive knowledge regarding the human brain by facilitating an extensive transcriptomic census across diverse brain regions. Nevertheless, understanding the cellular and temporal specificity of neurological disorders remains ambiguous due to developmental variations. To address this gap, we illustrated the dynamics of disorder risk gene expression under development by integrating multiple single-cell RNA sequencing datasets. We constructed a comprehensive single-cell atlas of the developing human brain, encompassing 393,060 single cells across diverse developmental stages. Temporal analysis revealed the distinct expression patterns of disorder risk genes, including those associated with autism, highlighting their temporal regulation in different neuronal and glial lineages. We identified distinct neuronal lineages that diverged across developmental stages, each exhibiting temporal-specific expression patterns of disorder-related genes. Lineages of nonneuronal cells determined by molecular profiles also showed temporal-specific expression, indicating a link between cellular maturation and the risk of disorder. Furthermore, we explored the regulatory mechanisms involved in early brain development, revealing enriched patterns of fetal cell types associated with neuronal disorders indicative of the prenatal stage’s influence on disease determination. Our findings facilitate unbiased comparisons of cell type‒disorder associations and provide insight into dynamic alterations in risk genes during development, paving the way for a deeper understanding of neurological disorders. The growth of the human brain is a complicated process that begins before birth and continues into young adulthood. Researchers focused on how genes related to brain disorders are expressed in different cells over time. They gathered data from 114 human brain samples, creating a single-cell atlas that traces brain growth from early fetal stages to adulthood. The results showed distinct patterns of gene expression linked to disorders like autism and developmental delay, especially in neurons during early growth. The study also emphasized the role of glial cells in brain conditions, such as Alzheimer’s and Parkinson’s disease, by showing specific gene expression patterns in these cells related to the disorders. Researchers conclude that their single-cell atlas greatly improves our understanding of brain growth and the molecular mechanisms behind brain disorders. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01328-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FTO-mediated SMAD2 m6A modification protects cartilage against Osteoarthritis","authors":"Hongyi Zhou,&nbsp;Ziang Xie,&nbsp;Yu Qian,&nbsp;Weiyu Ni,&nbsp;Lei Cui,&nbsp;Xiangqian Fang,&nbsp;Shuanglin Wan,&nbsp;Xiangde Zhao,&nbsp;An Qin,&nbsp;Shunwu Fan,&nbsp;Yizheng Wu","doi":"10.1038/s12276-024-01330-y","DOIUrl":"10.1038/s12276-024-01330-y","url":null,"abstract":"N6-methyladenosine (m6A) modification is one of the most prevalent forms of epigenetic modification and plays an important role in the development of degenerative diseases such as osteoarthritis (OA). However, the evidence concerning the role of m6A modification in OA is insufficient. Here, m6A modification was increased in human OA cartilage and degenerated chondrocytes. Among all of the m6A enzymes, the expression of the demethylase fat mass and obesity-associated protein (FTO) decreased dramatically. Conditional knockout of FTO in chondrocytes accelerates OA progression. FTO transcription is regulated by runt-related transcription factor-1 (RUNX1). Reduced FTO elevates m6A modification at the adenosine N6 position in SMAD family member 2 (SMAD2) mRNA, whose stability is subsequently modulated by the recruited m6A reader protein YTH N6-methyladenosine RNA binding protein F2 (YTHDF2). Collectively, these findings reveal the function and mechanism of the m6A family member FTO in OA progression. Therefore, reducing m6A modification to increase SMAD2 stability by activating FTO might be a potential therapeutic strategy for OA treatment. Osteoarthritis is a widespread joint disease-causing pain and disability. It involves the deterioration of joint cartilage and bone, but the exact reasons are unclear. This study aimed to investigate the role of a specific change in RNA molecules, called N6-methyladenosine, in OA development. The researchers focused on the enzyme FTO, which can remove this change, and its effect on cartilage cells in mice. They used different methods, including genetic modification to create mice lacking FTO in their cartilage cells, to see how changes in m6A levels affect OA progression. The main findings show that reducing FTO expression worsens OA progression by affecting the stability and function of specific RNA molecules in cartilage cells. The researchers conclude that targeting the m6A change pathway, especially by modulating FTO activity, could provide new treatment strategies for OA. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01330-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal fibroblasts are involved in fibrogenic changes in kidney fibrosis associated with dysfunctional telomeres","authors":"Sarita Saraswati,&nbsp;Paula Martínez,&nbsp;Rosa Serrano,&nbsp;Diego Mejías,&nbsp;Osvaldo Graña-Castro,&nbsp;Ruth Álvarez Díaz,&nbsp;Maria A. Blasco","doi":"10.1038/s12276-024-01318-8","DOIUrl":"10.1038/s12276-024-01318-8","url":null,"abstract":"Tubulointerstitial fibrosis associated with chronic kidney disease (CKD) represents a global health care problem. We previously reported that short and dysfunctional telomeres lead to interstitial renal fibrosis; however, the cell-of-origin of kidney fibrosis associated with telomere dysfunction is currently unknown. We induced telomere dysfunction by deleting the Trf1 gene encoding a telomere-binding factor specifically in renal fibroblasts in both short-term and long-term life-long experiments in mice to identify the role of fibroblasts in renal fibrosis. Short-term Trf1 deletion in renal fibroblasts was not sufficient to trigger kidney fibrosis but was sufficient to induce inflammatory responses, ECM deposition, cell cycle arrest, fibrogenesis, and vascular rarefaction. However, long-term persistent deletion of Trf1 in fibroblasts resulted in kidney fibrosis accompanied by an elevated urinary albumin-to-creatinine ratio (uACR) and a decrease in mouse survival. These cellular responses lead to the macrophage-to-myofibroblast transition (MMT), endothelial-to-mesenchymal transition (EndMT), and partial epithelial-to-mesenchymal transition (EMT), ultimately causing kidney fibrosis at the humane endpoint (HEP) when the deletion of Trf1 in fibroblasts is maintained throughout the lifespan of mice. Our findings contribute to a better understanding of the role of dysfunctional telomeres in the onset of the profibrotic alterations that lead to kidney fibrosis. Chronic kidney disease, a condition that can lead to kidney failure and death, affects millions worldwide. It’s characterized by kidney fibrosis, a process where healthy kidney tissue becomes scar tissue. The exact cells that start this process were unknown. Researchers studied the role of a protein called TRF1, which protects the ends of chromosomes, in kidney fibroblasts, cells that make connective tissue. They removed TRF1 from these cells in mice and observed the effects. Results showed that removing TRF1 from fibroblasts increased fibrosis, inflammation, and kidney damage. Specifically, fibroblasts without TRF1 were more likely to change into myofibroblasts, leading to more scar tissue. Study concluded that TRF1 is vital in preventing kidney fibrosis by keeping fibroblasts healthy. This finding improves our understanding of CKD and suggests potential treatments targeting fibroblasts and TRF1 to fight kidney fibrosis. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01318-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2","authors":"Yunju Jo,&nbsp;Hye-In Sim,&nbsp;Bohwan Yun,&nbsp;Yoon Park,&nbsp;Hyung-seung Jin","doi":"10.1038/s12276-024-01317-9","DOIUrl":"10.1038/s12276-024-01317-9","url":null,"abstract":"Cancer immunotherapy aims to initiate or amplify immune responses that eliminate cancer cells and create immune memory to prevent relapse. Immune checkpoint inhibitors (ICIs), which target coinhibitory receptors on immune effector cells, such as CTLA-4 and PD-(L)1, have made significant strides in cancer treatment. However, they still face challenges in achieving widespread and durable responses. The effectiveness of anticancer immunity, which is determined by the interplay of coinhibitory and costimulatory signals in tumor-infiltrating immune cells, highlights the potential of costimulatory receptors as key targets for immunotherapy. This review explores our current understanding of the functions of CD2 and CD226, placing a special emphasis on their potential as novel agonist targets for cancer immunotherapy. CD2 and CD226, which are present mainly on T and NK cells, serve important functions in cell adhesion and recognition. These molecules are now recognized for their costimulatory benefits, particularly in the context of overcoming T-cell exhaustion and boosting antitumor responses. The importance of CD226, especially in anti-TIGIT therapy, along with the CD2‒CD58 axis in overcoming resistance to ICI or chimeric antigen receptor (CAR) T-cell therapies provides valuable insights into advancing beyond the current barriers of cancer immunotherapy, underscoring their promise as targets for novel agonist therapy. Immunotherapy, including immune checkpoint inhibitors and adoptive T-cell therapy, has transformed cancer treatment, yet durable responses are limited to a minority of patients. Anticancer immunity, shaped by co-inhibitory and co-stimulatory signals in tumor-infiltrating immune cells, underscores co-stimulatory receptors as promising targets for immunotherapy. This review explores the roles of CD226 and CD2 in regulating T cell responses, particularly in tumor immunity. CD2 and CD226, primarily on T and NK cells, are crucial for cell adhesion and recognition, known for their role in overcoming T cell exhaustion and boosting anti-tumor responses. The review examines their potential as targets in novel cancer immunotherapeutic strategies. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01317-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}