Journal of Molecular Medicine-Jmm最新文献

{"title":"Role of aberrant activated fibro/adipogenic progenitors and suppressed ferroptosis in disused skeletal muscle atrophy and fatty infiltration.","authors":"Jiale Tan, Yuqi Li, Jie Zhang, Beijie Qi, Jiwu Chen, Yaying Sun","doi":"10.1007/s00109-025-02548-7","DOIUrl":"10.1007/s00109-025-02548-7","url":null,"abstract":"<p><p>Muscle fatty infiltration (MFI) was characterized by the pathological accumulation of fat within skeletal muscle tissue. Previous studies have found that the progress of this pathological phenomenon in aging, acute muscle injury, and other conditions was triggered by the activation and adipogenic differentiation of the key cell population, fibro/adipogenic progenitors (FAPs), but there were few studies on the fat infiltration caused by disused skeletal muscle atrophy, and the regulatory role of FAPs in this situation has not been deeply explored, leaving the related molecular mechanisms still unknown. In this study, we conducted single-cell RNA sequencing on the disused skeletal muscle. The aberrant proliferation of FAPs in this state was found by subsequent analysis, along with the high expression of the ferroptosis inhibitory gene in the activated FAPs. By immunofluorescence staining, we verified the proliferation and adipogenic differentiation of FAPs, which proved the role of FAPs in fat infiltration of disused skeletal muscle. In order to further verify the relationship between ferroptosis inhibition and FAPs activation/adipogenic differentiation, we used ferrostatin-1, a commonly used ferroptosis inhibitor, to treat skeletal muscle fibroblasts and FAPs in vitro, and verified the enhancement of ferroptosis inhibition on their adipogenic/fibrogenic ability. Our study pinpointed the effect of aberrant activation of FAPs on MFI in disused skeletal muscle, and preliminarily recognized the potential effect of ferroptosis on the adipogenic differentiation of FAPs. KEY MESSAGES: • Muscle fatty infiltration (MFI) was characterized by the pathological accumulation of fat within skeletal muscle. Fibro/adipogenic progenitors (FAPs) were thought to be crucial regulators of MFI, but their correlations in disused skeletal muscle were unspecified. • In this study, we conducted single-cell RNA sequencing on the disused skeletal muscle and recognized the aberrant proliferation of FAPs along with the upregulated ferroptosis inhibition genes in this status. • Subsequently, we used ferrostatin-1 (ferroptosis inhibitor) to treat skeletal muscle fibroblasts in vitro, and verified the enhancement of ferroptosis inhibition on their adipogenic/fibrogenic ability. • Our study pinpointed the effect of aberrant activation of FAPs on MFI in disused skeletal muscle, and preliminarily recognized the potential effect of ferroptosis on the adipogenic differentiation of FAPs.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"713-724"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New mesenchymal stem/stromal cell-based strategies for osteoarthritis treatment: targeting macrophage-mediated inflammation to restore joint homeostasis.","authors":"María Jesús Araya-Sapag, Eliana Lara-Barba, Cynthia García-Guerrero, Yeimi Herrera-Luna, Yesenia Flores-Elías, Felipe A Bustamante-Barrientos, Guillermo G Albornoz, Consuelo Contreras-Fuentes, Liliana Yantén-Fuentes, Noymar Luque-Campos, Ana María Vega-Letter, Jorge Toledo, Patricia Luz-Crawford","doi":"10.1007/s00109-025-02547-8","DOIUrl":"10.1007/s00109-025-02547-8","url":null,"abstract":"<p><p>Macrophages are pivotal in osteoarthritis (OA) pathogenesis, as their dysregulated polarization can contribute to chronic inflammatory processes. This review explores the molecular and metabolic mechanisms that influence macrophage polarization and identifies potential strategies for OA treatment. Currently, non-surgical treatments for OA focus only on symptom management, and their efficacy is limited; thus, mesenchymal stem/stromal cells (MSCs) have gained attention for their anti-inflammatory and immunomodulatory capabilities. Emerging evidence suggests that small extracellular vesicles (sEVs) derived from MSCs can modulate macrophage function, thus offering potential therapeutic benefits in OA. Additionally, the transfer of mitochondria from MSCs to macrophages has shown promise in enhancing mitochondrial functionality and steering macrophages toward an anti-inflammatory M2-like phenotype. While further research is needed to confirm these findings, MSC-based strategies, including the use of sEVs and mitochondrial transfer, hold great promise for the treatment of OA and other chronic inflammatory diseases.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"651-669"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of disease and species differences on the intestinal CLCA4 gene expression.","authors":"K Teske, N A Erickson, A Huck, M Dzamukova, M Fulde, T Heinbokel, D Horst, N Klymiuk, E Pastille, A Mekes-Adamczyk, M Löhning, A D Gruber, R Glauben, L Mundhenk","doi":"10.1007/s00109-025-02538-9","DOIUrl":"10.1007/s00109-025-02538-9","url":null,"abstract":"<p><p>The human chloride channel regulator, calcium-activated (CLCA) 4 is discussed as a driver of epithelial-to-mesenchymal transition as well as a biomarker for colorectal cancer (CRC) and ulcerative colitis. In contrast to humans, the Clca4 gene is duplicated in the mouse, a common model species to study gene functions. However, the relevance of the functional murine Clca4 variants in healthy and diseased intestine is largely unknown. Here, we characterized the spatiotemporal expression patterns of the murine Clca4a and Clca4b genes in the healthy intestinal tract as well as in dextran sulfate sodium (DSS)-induced colitis and colitis-associated colon cancer (CAC) mouse model using RT-qPCR and in situ-hybridization. Similarly, we analyzed expression of the human CLCA4 in healthy, inflamed and cancerous intestinal tracts at single cell level. Murine Clca4a and -4b but not the human CLCA4 were detected in small intestine enterocytes of the respective species. Conversely, healthy colonocytes expressed the human CLCA4 and its murine ortholog Clca4a but not the murine Clca4b. Under inflammatory conditions, de novo expression of Clca4b was observed with both murine homologs abundantly expressed in enterocytes adjacent to ulcerations. Neoplastic colonocytes expressed none or only minimal amounts of the CLCA4 homologs both in humans and mice, whereas adjacent non-neoplastic colonocytes strongly up-regulated the human or both murine homologs, respectively. Our results suggest marked species- and homolog-specific differences in the expression patterns of the three CLCA4 homologs. Moreover, all three seem to play a role in reactive, non-neoplastic colonocytes adjacent to ulcerated and neoplastic lesions. KEY MESSAGES: Human CLCA4 and murine Clca4a, but not Clca4b, are expressed in healthy colonocytes. Inflammation leads to a de novo expression of the murine Clca4b in colonocytes. Human and murine CLCA4 homologs are absent from neoplastic enterocytes. Human and murine CLCA4s are highly expressed in tumor-adjacent, reactive colonocytes.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"687-697"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review of m6 A methylation in coronary heart disease.","authors":"Mei-Ning Diao, Yi-Jv Lv, Hui Xin, Yin-Feng Zhang, Rui Zhang","doi":"10.1007/s00109-025-02540-1","DOIUrl":"10.1007/s00109-025-02540-1","url":null,"abstract":"<p><p>The morbidity and mortality rates of coronary heart disease (CHD) are high worldwide. The primary pathological changes in CHD involve stenosis and ischemia caused by coronary atherosclerosis (AS). Extensive research on the pathogenesis of AS has revealed chronic immunoinflammatory processes and cell proliferation in all layers of coronary vessels, including endothelial cells (ECs), vascular smooth muscle cells, and macrophages. m6 A methylation is a common posttranscriptional modification of RNA that is coordinated by a variety of regulators (writers, readers, erasers) to maintain the functional stability of modified mRNAs and ncRNAs. In recent years, there has been increasing focus on the involvement of m6 A methylation in the incidence and progression of CHD, which starts with atherosclerotic plaque formation, leads to myocardial ischemia, and ultimately results in the occurrence of myocardial infarction (MI). m6 A regulators modulate relevant signaling pathways to participate in the inflammatory response, programmed death of cardiomyocytes, and fibrosis. Therefore, diagnostic models based on m6 A profiling are helpful for the early detection of CHD, and m6 A methylation shows promise as a sensitive target for new drugs to treat CHD in the future.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"619-633"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring endothelial dysfunction in major rheumatic diseases: current trends and future directions.","authors":"Arshiya S Anwar Husaini, Aseela Fathima, Dunia Halawa, Nada Aakel, Gian Luca Erre, Roberta Giordo, Hatem Zayed, Gianfranco Pintus","doi":"10.1007/s00109-025-02539-8","DOIUrl":"10.1007/s00109-025-02539-8","url":null,"abstract":"<p><p>The relationship between rheumatic diseases (RDs) and endothelial dysfunction (ED) is intricate and multifaceted, with chronic inflammation and immune system dysregulation playing key roles. RDs, including Osteoarthritis (OA), Rheumatoid arthritis (RA), Systemic Lupus erythematosus (SLE), Ankylosing spondylitis (AS), Psoriatic arthritis (PsA), Sjogren's syndrome (SS), Systemic sclerosis (SSc), Polymyalgia rheumatica (PMR) are characterized by chronic inflammation and immune dysregulation, leading to ED. ED is marked by reduced nitric oxide (NO) production, increased oxidative stress, and heightened pro-inflammatory and prothrombotic activities, which are crucial in the development of cardiovascular disease (CVD) and systemic inflammation. This association persists even in RD patients without conventional cardiovascular risk factors, suggesting a direct impact of RD-related inflammation on endothelial function. Studies also show that ED significantly contributes to atherosclerosis, thereby elevating cardiovascular risk in RD patients. This review synthesizes the molecular mechanisms connecting major RDs and ED, highlighting potential biomarkers and therapeutic targets. Ultimately, the review aims to enhance understanding of the complex interactions leading to ED in rheumatic patients and inform strategies to mitigate cardiovascular risks and improve patient outcomes.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"635-649"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased IL- 36γ in visceral adipose tissue as a key mediator of obesity-driven inflammation in colon cancer.","authors":"Gema Frühbeck, Sofía Criado, Javier Gómez-Ambrosi, Beatriz Ramírez, Sara Becerril, Amaia Rodríguez, Gabriela Neira, Laura Salmón-Gómez, Víctor Valentí, Rafael Moncada, Jorge Baixauli, Camilo Silva, Victoria Catalán","doi":"10.1007/s00109-025-02546-9","DOIUrl":"10.1007/s00109-025-02546-9","url":null,"abstract":"<p><p>Dysfunctional adipose tissue (AT) in the context of obesity promotes a chronic inflammatory state, associated with worse cancer progression and prognosis. Interleukin (IL)-36γ is a proinflammatory factor increased in obesity. The aim was to analyse the role of IL-36γ in colon cancer (CC) development in patients with obesity. Samples obtained from 74 volunteers (27 with normal weight (NW) and 47 with obesity (OB)) were used in a case-control study. Participants were also subclassified according to the presence of CC (45 without and 29 with CC). HT-29 cells were treated with pro-inflammatory factors, adipocyte conditioned media (ACM) and IL-36γ to evaluate the expression levels of inflammation- and extracellular matrix (ECM) remodelling-related molecules. Increased gene expression levels of IL36G and IL36R in visceral AT from patients with OB and CC were found. Moreover, mRNA levels of IL36G were significantly associated with the gene expression levels of its receptor and relevant genes involved in AT inflammation (ASC, IL1B and NLRP6). Consistently, IL36G expression was upregulated by hypoxia, inflammation-related factors (LPS, TNF-α and leptin) and by the adipocyte secretome from patients with obesity in HT-29 cancer cells. Furthermore, we revealed that IL-36γ increased the gene expression levels of inflammation-related genes (IL36G, IL1 A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells. Increased gene expression levels of IL36G in VAT from patients with OB and CC may promote a pro-inflammatory microenvironment favourable for tumour progression and migration. KEY MESSAGES: Obesity and colon cancer increase gene expression levels of IL36G and IL36R in visceral adipose tissue. Hypoxia, inflammation-related factors and the adipocyte secretome from patients with obesity upregulate mRNA levels of IL36G in HT-29 cancer cells. IL-36γ increase the gene expression levels of inflammation-related genes (IL36G, IL1A, IL1B, IL6, IL8 and NGAL) as well as ECM markers (MMP9, SPP1 and TNC) in HT-29 cells.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"699-711"},"PeriodicalIF":4.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications.","authors":"Litao Chen, Lechen Hu, Han Chang, Jianing Mao, Meng Ye, Xiaofeng Jin","doi":"10.1007/s00109-025-02533-0","DOIUrl":"10.1007/s00109-025-02533-0","url":null,"abstract":"<p><p>Cytoplasmic DNA-RNA hybrids are emerging as important immunogenic nucleic acids, that were previously underappreciated. DNA-RNA hybrids, formed during cellular processes like transcription and replication, or by exogenous pathogens, are recognized by pattern recognition receptors (PRRs), including cGAS, DDX41, and TLR9, which trigger immune responses. Post-translational modifications (PTMs) including ubiquitination, phosphorylation, acetylation, and palmitoylation regulate the activity of PRRs and downstream signaling molecules, fine-tuning the immune response. Targeting enzymes involved in DNA-RNA hybrid metabolism and PTMs regulation offers therapeutic potential for inflammatory diseases. Herein, we discuss the sources, immune response, and therapeutic implications of DNA-RNA hybrids in inflammation, highlighting the significance of DNA-RNA hybrids as potential targets for the treatment of inflammation.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"511-529"},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare and low-frequency variants in families with otitis media.","authors":"Regie Lyn P Santos-Cortez, Christina L Elling, Helen Z Gomez, Elisabet Einarsdottir, Juha Kere, Petri S Mattila, Lena Hafrén, Allen F Ryan","doi":"10.1007/s00109-025-02537-w","DOIUrl":"10.1007/s00109-025-02537-w","url":null,"abstract":"<p><p>Otitis media is a highly frequent diagnosis in children that causes significant morbidity but remains understudied as a genetic trait despite significant heritability in families. To identify rare or low-frequency variants within genes that confer susceptibility to otitis media, exome sequence data of 287 individuals from 243 families were analyzed. Identified variants were tested for co-segregation with otitis media in family members. Genome sequence data from a case-control cohort was imputed and analyzed for association of specific genes with otitis media. Single-cell RNA-sequence data of identified genes were noted in acutely infected mouse middle ears. Thirty-three variants within 24 genes co-segregated with otitis media in 28 families, of which 18 variants were considered pathogenic or likely pathogenic. An additional 81 variants in 21 of the same genes were identified in 83 unrelated probands with otitis media. Of the 24 genes, 12 were associated with otitis media in mouse models, while 15 genes were replicated from previous human studies. A common variant EYA4 c.829G > A was associated with OM in the case-control cohort. Using network analysis, 22 of the 24 genes were connected in a subnetwork enriched in various signaling pathways, Th1/Th2/Th17 cell differentiation, and viral infections. Majority (87.5%) of the identified genes were expressed in mouse middle ear cells, with differential expression after acute infection. The identification of novel genes and variants for susceptibility to otitis media will be useful in future risk screening and clinical management in children that require a more personalized approach due to poor response to standard treatments. KEY MESSAGES: Thirty-three variants in 24 genes were identified in 28 families with otitis media. Eighteen of these variants within 10 genes were considered (likely) pathogenic. A common variant EYA4 c.829G > A was associated with OM in a case-control cohort. The novel genes were differentially expressed in mouse middle ear post-infection. Genetic screening could identify children for targeted treatment for otitis media.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"559-570"},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ONC201 exerts oncogenic effects beyond its mitochondria-disturbing role in neuroblastoma subsets.","authors":"Jyun-Hong Jiang, Yu-Han Lin, Pei-Lin Liao, Ting-Ya Chen, Hui-Ching Chuang, Chao-Cheng Huang, Wen-Ming Hsu, Jiin-Haur Chuang, Wei-Shiung Lian","doi":"10.1007/s00109-025-02541-0","DOIUrl":"10.1007/s00109-025-02541-0","url":null,"abstract":"<p><p>Neuroblastoma (NB) is a formidable challenge in pediatric oncology due to its intricate molecular landscape, necessitating multifaceted therapeutic approaches. ONC201 is an imipridone antibiotic compound with a promising drug candidate leveraging its potent anticancer properties against the mitochondrial proteases ClpP and ClpX. Despite demonstrating early clinical promise, particularly in MYCN-amplified NB, its efficacy in non-MYCN-amplified NB remains a subject worthy of investigation. In this study, we extended the coverage of ONC201 to treat non-MYCN-amplified NB, and our data implicated ONC201's inability to reduce tumor growth in animal models harboring SK-N-AS or SK-N-FI cell lines. Interestingly, ONC201 induced the expression of oncogenic markers c-Myc and LGR5 while downregulating the tumor suppressor ATRX. While it fails to attenuate tumor neovascularization in non-MYCN-amplified NB xenografts, its effectiveness differs from that of its MYCN-amplified counterpart. Rho zero (ρ0)-SK-N-AS cells treated with ONC201 showed comparable observed trends in parental SK-N-AS cells, including LGR5 upregulation and ATRX downregulation, suggesting that ONC201's multifaceted actions extend beyond mitochondrial targets. Our elucidation highlights the need to discern molecular signatures when deploying ONC201 monotherapy against NB, which lacks MYCN-amplification.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":"103 5","pages":"571-582"},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of innate lymphoid cell by microbial metabolites.","authors":"Hongji Tao, Jingjing Geng, Long Bai, Dan Su, Yu Zhao, Guifang Xu, Mingming Zhang","doi":"10.1007/s00109-025-02530-3","DOIUrl":"10.1007/s00109-025-02530-3","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) are a unique category of immune cell that lack antigen-specific receptors yet possess the capacity to detect signals from the surrounding tissue. The majority of ILCs reside in the lymphoid and mucosal tissues, maintaining close associations with the microbiota. Beyond the contributions of accessory cells and adaptive immune cells, accumulating studies demonstrate that microbial metabolites serve a crucial role in mediating the relationship between ILCs and the microbiota. In this review, we highlight and summarize the roles of microbial metabolites from different sources in modulating ILC subsets, proposing these metabolites as potential therapeutic mechanisms in ILC-mediated diseases.</p>","PeriodicalId":50127,"journal":{"name":"Journal of Molecular Medicine-Jmm","volume":" ","pages":"491-509"},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}