The FASEB Journal最新文献

{"title":"Exploring the Role of Oral Microbiota in the Pathophysiology and Treatment of Bruxism","authors":"Kyle Morris,&nbsp;Karima Ait-Aissa,&nbsp;Amal M. Sahyoun,&nbsp;Qi Wang,&nbsp;Ammaar H. Abidi,&nbsp;Modar Kassan","doi":"10.1096/fj.202502015R","DOIUrl":"10.1096/fj.202502015R","url":null,"abstract":"<p>Bruxism is an involuntary condition involving grinding and clenching of the teeth, occurring during both wakefulness and sleep. This behavior can lead to various detrimental effects on oral health, including significant tooth wear and damage, temporomandibular disorders (TMD), tooth sensitivity, gum recession, and persistent headaches along with ear pain or tinnitus. The underlying causes of bruxism have long been debated, with the consensus suggesting that psychological, genetic, and environmental factors contribute to its development. Traditionally, the etiology of bruxism has been linked to stress, anxiety, malocclusion or dental misalignment, and other behavioral factors. However, recent research has begun to explore the potential role of oral microbiota in the pathophysiology of bruxism. Emerging studies propose that disruptions in the balance of oral bacteria may influence the onset and severity of bruxism, possibly by affecting inflammatory processes or neurological pathways related to muscle function. This literature review aims to explore this novel connection, summarizing key study findings, examining the implications for treatment, and evaluating the potential mechanisms by which oral microbiota may impact bruxism. Understanding this relationship could open new avenues for therapeutic strategies targeting microbial factors in managing bruxism.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202502015R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFN-γ Targeting the JAK2/STAT3-METTL3 Pathway Ameliorates Mandibular Osteogenic Differentiation in Postmenopausal Rats","authors":"Shan-shan Yang,&nbsp;Xiao-hua Hu,&nbsp;Rong Zhou,&nbsp;Rui-xin Wang,&nbsp;Xiao-hong Yang","doi":"10.1096/fj.202500931R","DOIUrl":"10.1096/fj.202500931R","url":null,"abstract":"<div>\u0000 \u0000 <p>To investigate whether interferon-gamma (IFN-γ) alleviates postmenopausal osteoporosis (POP) by regulating METTL3 via the JAK2/STAT3 pathway to enhance osteogenic differentiation of jawbone marrow stromal cells (JBMSCs). Ovariectomized (OVX) rats received IFN-γ (5000 IU/dose, 3×/week for 24 weeks), with jawbone mass assessed via micro-CT and HE staining. JBMSCs were cultured, and osteogenic differentiation under IFN-γ (optimal concentration: 10 ng/mL) was evaluated using qRT-PCR, ALP/alizarin red staining, and CCK-8. METTL3's role was analyzed via lentiviral overexpression (OE-METTL3) or knockdown (sh-METTL3). JAK2/STAT3 pathway activity was tested using AG490 (JAK2 inhibitor) and Western blot for phosphorylated JAK2/STAT3. IFN-γ reduced alveolar bone loss in OVX rats, increased osteocytes, and decreased osteoclasts. In JBMSCs, 10 ng/mL IFN-γ upregulated osteogenic genes (Runx2, OPN, OPG) and mineralization. METTL3 expression was elevated by IFN-γ; sh-METTL3 suppressed Runx2, while OE-METTL3 reversed OVX-induced osteogenic inhibition. IFN-γ activated JAK2/STAT3 signaling, but AG490 reduced both osteogenic gene expression and METTL3 levels. METTL3 overexpression amplified JAK2/STAT3 phosphorylation, synergizing with IFN-γ to enhance osteogenesis. IFN-γ activates the JAK2/STAT3 pathway to drive METTL3 transcription, upregulating osteogenic genes and mitigating jawbone loss in POP. METTL3 overexpression counteracts estrogen deficiency-induced osteogenic suppression and forms a positive feedback loop with JAK2/STAT3. AG490's complete blockade of IFN-γ/METTL3 effects confirms the JAK2/STAT3-METTL3 axis as central to bone immune metabolism, highlighting therapeutic potential for targeting this pathway in POP.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Genomics and Phenotypic Profiling Reveal Lacticplantibacillus plantarum BGI-N6 as a Multifunctional Candidate for Dermatological Probiotic Development","authors":"Jinhong Wang,&nbsp;Xiaowei Xu,&nbsp;Yangfeng Wen,&nbsp;Benliang Wei,&nbsp;Junke Chen,&nbsp;Sihang Cai,&nbsp;Mengmeng Wang,&nbsp;Zhinan Wu,&nbsp;Yanhong Liu,&nbsp;Haifeng Zhang,&nbsp;Yiyi Zhong,&nbsp;Yuanqiang Zou","doi":"10.1096/fj.202501440R","DOIUrl":"10.1096/fj.202501440R","url":null,"abstract":"<div>\u0000 \u0000 <p>Probiotics and postbiotics are recognized for their potential to benefit skin health, and complete genome analysis serves as a pivotal tool to accelerate the exploration of probiotic functionalities. To investigate this relationship, this study aimed to elucidate the skin-promoting potential of <i>Lactiplantibacillus plantarum</i> BGI-N6 (BGI-N6) through integrated genomic analysis and phenotypic analysis. Results indicated that the high-precision complete genome of BGI-N6 comprises 3 257 641 bases with a 45% GC content and 3030 CDSs, involving multiple genes related to carbon source fermentation, gastrointestinal tolerance, and environmental adaptability. Notably, BGI-N6 possessed several bacteriostatic, antioxidant, and enzyme activity inhibition-related genes, which could encode the biosynthetic pathways of bacteriocins, glutathione/thioredoxin antioxidant systems, NADH peroxidase, catalase, and various organic acids. Supporting these genomic insights, in vitro experiments comparative evaluation revealed that BGI-N6 exhibited superior capabilities relative to <i>Lactiplantibacillus plantarum</i> 299v (299v) in antioxidant activity, inhibition of cutaneous pathogens growth, and suppression of skin-damaging enzyme (e.g., collagenase and elastase) activity. These effects were correlated with the production of lactic acid, 6-hydroxyhexanoate, coumarins, and other bioactive compounds by BGI-N6. The evidence from integrated genomic analysis and in vitro experiments established a critical theoretical foundation for the development of BGI-N6 as a candidate for probiotic and postbiotic applications targeting skin health.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Molecular Crowding in Repair Foci Surrounding DNA Breaks, Measured by Fluorescence Lifetime Imaging Microscopy","authors":"Svitlana M. Levchenko,&nbsp;Jurek W. Dobrucki","doi":"10.1096/fj.202501727R","DOIUrl":"10.1096/fj.202501727R","url":null,"abstract":"<p>The density of mammalian cells is determined primarily by the protein content. Local concentration of proteins in a cell is tightly controlled and varies between the cytoplasm, nucleoplasm, and nucleoli. We demonstrate that repair foci that are formed in response to DNA breaks are much more densely packed with proteins than the surrounding nucleoplasm. Using fluorescence lifetime imaging (FLIM), we demonstrated that the local concentration of all proteins (i.e., the residing and recruited ones) in double- and single-strand DNA repair foci can be even 2.2 times higher than that in the surrounding nucleoplasm, which brings them close to the achievable maximum concentration. The highest protein density is found in the center of a repair focus and gradually decreases with distance from the DNA lesion. We hypothesize that a microenvironment characterized by such a high protein concentration may facilitate the formation of protein condensates, resulting in the stabilization of repair complexes.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202501727R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Pro-Angiogenic and Pro-Fibrotic MARCO+ Microglial Phenotype in Diabetic Retinopathy","authors":"Qinyuan Gu,&nbsp;Xiying Mao,&nbsp;Jingyi Xu,&nbsp;Pengfei Ge,&nbsp;Xinjing Wu,&nbsp;Chengkun Wang,&nbsp;Jingfan Wang,&nbsp;Hongying Li,&nbsp;Yuanyuan Fan,&nbsp;Tianhao Xiao,&nbsp;Qinghuai Liu,&nbsp;Ping Xie,&nbsp;Zizhong Hu","doi":"10.1096/fj.202502138R","DOIUrl":"10.1096/fj.202502138R","url":null,"abstract":"<div>\u0000 \u0000 <p>Proliferative diabetic retinopathy (PDR) is a complication of diabetic microangiopathy that can cause severe visual impairment. Due to retinal neovascularization and fibrovascular membrane (FVM) formation, inhibition of vascularization and fibrosis plays a key role in PDR. In our study, single-cell sequencing of FVMs from PDR patients identified a MARCO⁺ microglial subpopulation exhibiting both pro-angiogenic and pro-fibrotic effects. In vitro experiments demonstrated that glycated albumin (GA) significantly upregulated MARCO expression in BV2 cells in a dose-dependent manner. In vivo experiments, oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models were established in wild-type (WT) and MARCO⁻/⁻ mice. The accumulation of MARCO⁺ microglia promoted retinal angiogenesis and fibrogenesis in WT mouse models, but not in MARCO⁻/⁻ mouse models. Mechanistically, next-generation sequencing confirmed that the activation of the TLR4/NF-κB signaling pathway results in the increased expression of MARCO⁺ microglia. Furthermore, the targeted drug PolyG, which inhibits MARCO⁺ microglia, resulted in reduced angiogenesis and fibrogenesis in mouse models. Taken together, we demonstrate that MARCO⁺ microglia could be a potential therapeutic target for ocular angiogenic and fibrotic diseases.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of HDAC9 Alleviates Autophagy Dysfunction by Inducing Acetylation of ATG4B in Metabolic Dysfunction-Associated Steatotic Liver Disease","authors":"Xiao-Han Ma,&nbsp;Guang-Peng Liu,&nbsp;Le Liu,&nbsp;Zi-yue Dou,&nbsp;Xue He,&nbsp;Xi Chen","doi":"10.1096/fj.202501627R","DOIUrl":"10.1096/fj.202501627R","url":null,"abstract":"<div>\u0000 \u0000 <p>Metabolic dysfunction–associated steatotic liver disease (MASLD) is a prevalent hepatic metabolic disorder with a rising global incidence. Epigenetic modifications—such as methylation, acetylation, phosphorylation, and ubiquitination—play critical roles in the initiation and progression of MASLD. This study utilized two datasets, GSE89632 and GSE202379. By intersecting 2602 differentially expressed genes (DEGs) with 720 epigenetic factor-related genes (EF-RGs), 91 candidate genes were identified. Protein–protein interaction (PPI) network analysis, machine learning, and single-cell sequencing collectively identified HDAC9 as the hub gene. HDAC9 was found to be highly expressed in db/db mice and patients with MASLD and positively correlated with liver enzymes and serum lipids in patients with MASLD. Loss-of-function experiments confirmed its pathogenic role in MASLD in both in vitro and in vivo models. Silencing HDAC9 reduced the severity of fibrosis and inflammation, while also alleviating autophagy dysfunction in db/db mice and palmitic acid–treated human liver sinusoidal endothelial cells (hLSECs). Mechanistically, HDAC9 was shown to decrease H3K9 acetylation at the promoter region of ATG4B, a key autophagy regulator, thereby suppressing ATG4B transcription and impairing autophagy in MASLD. In conclusion, this study demonstrates that HDAC9 expression increases alongside clinical indicators of MASLD, and HDAC9 knockdown alleviates fibrosis and inflammation and restores autophagy by enhancing ATG4B acetylation. Therefore, HDAC9 may serve as a potential biomarker for the prevention and treatment of MASLD.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ApoE Mimetic Peptide-MsrA Fusion Protein Restores HDL Function and Ameliorates Atherosclerosis via Circulatory Redox Remodeling in SR-BI Deficient Mice","authors":"Yu Liu,&nbsp;Jun-Xing Pu,&nbsp;Xin Yang,&nbsp;Mu-Chuan Liu,&nbsp;Peng Zhang,&nbsp;Jia Cao,&nbsp;Fen Du,&nbsp;Dong-Fang Wu,&nbsp;Zhi-Bing Lu,&nbsp;Hong Yu","doi":"10.1096/fj.202501588R","DOIUrl":"10.1096/fj.202501588R","url":null,"abstract":"<div>\u0000 \u0000 <p>The redox imbalance in circulation can lead to inflammation and cellular damage in vascular walls, which plays a crucial role in atherogenesis. We previously designed an apolipoprotein E (ApoE) mimetic peptide, EpK, which can reduce atherosclerosis in ApoE-deficient mice by binding high-density lipoprotein (HDL). Meanwhile, hepatic overexpression of methionine sulfoxide reductase A (MsrA) can exert indirect anti-atherosclerotic effects. Therefore, exploring biomolecules that directly promote circulatory redox rebalance is significant for the therapy of atherosclerotic cardiovascular diseases (ASCVD). MsrA was recombined with EpK to achieve the secretory expression of EpK-MsrA. Our experiments revealed that EpK and EpK-MsrA significantly improved the oxidative state and inflammatory composition of dysfunctional HDL and promoted hepatic cholesterol uptake and excretion, thereby alleviating atherosclerosis and hepatic steatosis in scavenger receptor class B type I deficient (SR-BI^−/−) mice. Furthermore, compared with EpK, EpK-MsrA had a stronger anti-inflammatory and regulatory effect on HDL functional proteins, such as apolipoprotein AI (ApoAI), paraoxonase 1 (PON1), and lecithin cholesterol acyltransferase (LCAT), thereby further reducing atherosclerosis. Additionally, exogenous EpK-MsrA may be able to regenerate its antioxidant activity through EpK recycling. This study suggests that novel secreted EpK-MsrA can combine the different antioxidant mechanisms of EpK and MsrA, significantly improve the functional proteins related to lipid metabolism and inflammation, and effectively alleviate atherosclerosis in SR-BI^−/− mice, which may be a promising strategy for the treatment of ASCVD.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"11-Methoxytabersonine Induces Ferroptosis in Triple-Negative Breast Cancer via YY1–CDKL1–GPX4 Axis","authors":"Di Zhang,&nbsp;Zhen Meng,&nbsp;Dongyan Zhang,&nbsp;Yan Wang,&nbsp;Miaomiao Chu,&nbsp;Jun Li,&nbsp;Jianran Guo,&nbsp;Chunpeng Xia,&nbsp;Yujiao Liu,&nbsp;Cheng Chen,&nbsp;Chuanbao Wang,&nbsp;Lei Fang,&nbsp;Bo Fu","doi":"10.1096/fj.202502087R","DOIUrl":"10.1096/fj.202502087R","url":null,"abstract":"<div>\u0000 \u0000 <p>The 11-Methoxytabersonine (11-MT), a monoterpenoid-indole alkaloid isolated from the leaves of Melodinus henryi, has shown promising therapeutic potential against triple-negative breast cancer (TNBC). This study aimed to evaluate the anti-tumor efficacy of 11-MT and to elucidate its underlying molecular mechanisms in the context of TNBC. The in vitro anti-cancer effects of 11-MT were assessed using Cell Counting Kit-8 (CCK-8), colony formation assays, and flow cytometry. In vivo efficacy and safety were evaluated in a xenograft mouse model using 7-week-old female BALB/cA-nu nude mice. To explore the potential of 11-MT in inducing ferroptosis, transmission electron microscopy (TEM), reactive oxygen species (ROS) detection, mitochondrial membrane potential (MMP) assays, and analysis of glutathione peroxidase 4 (GPX4) expression were conducted. Mechanistic investigations included lentiviral-mediated knockdown of Yin Yang 1 (YY1) and overexpression of cyclin-dependent kinase-like 1 (CDKL1), as well as co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and a series of rescue experiments to delineate the regulatory effect of 11-MT on GPX4 expression. The 11-MT significantly inhibited TNBC cell proliferation, induced cell cycle arrest, and promoted cell death in vitro. In vivo, treatment with 11-MT significantly suppressed tumor growth in TNBC xenograft models without evident toxicity to major organs. Mechanistic studies revealed that 11-MT primarily triggered ferroptosis through downregulation of GPX4, leading to excessive ROS accumulation independent of intracellular glutathione depletion. Furthermore, 11-MT reduced the expression of transcription factor YY1, suppressing CDKL1 transcription, which in turn led to the downregulation of GPX4. In summary, the results revealed that the 11-MT exerts potent anti-tumor activity against TNBC by inducing ferroptosis via the YY1–CDKL1–GPX4 signaling axis, highlighting its potential as a novel therapeutic agent for the treatment of TNBC.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Strategy for Preparation of ADSCs-Osteogenic Microtissue Based on CEFFE and Mechanisms for Enhancing Osteogenic Activity","authors":"Mengqi Nie,&nbsp;Xizhe Li,&nbsp;Yutian Xiao,&nbsp;Shaorong Lei,&nbsp;Dingyu Wu","doi":"10.1096/fj.202502341R","DOIUrl":"10.1096/fj.202502341R","url":null,"abstract":"<div>\u0000 \u0000 <p>Adipose-derived mesenchymal stem cells (ADSCs) are more accessible than bone marrow mesenchymal stromal cells but have limited osteogenic differentiation capabilities in bone tissue engineering. Cell-free fat extract (CEFFE) from adipose tissue shows promise in enhancing the osteogenesis of ADSCs. This study aimed to investigate the impact of CEFFE on ADSCs and its role in promoting ADSC osteogenic activity both in vitro and in vivo. CEFFE was obtained and characterized. In vitro, ADSCs were isolated, characterized, and analyzed using various assays. Osteogenic differentiation was quantified through staining and gene expression analysis. ADSC-based osteogenic microtissues with CEFFE were created and tested in nude mice models. Molecular mechanisms were explored through transcriptomic analysis and western blotting. CEFFE enhanced various osteogenic aspects of ADSCs, including proliferation, calcium nodule formation, and expression of osteogenic markers. CEFFE-treated ADSCs showed early dense osteogenic cell sheet formation and increased ectopic bone volume in mice. Transcriptomic analysis revealed upregulation/downregulation of genes and activation of the PI3K-Akt signaling pathway by CEFFE. Western blotting confirmed that the PI3K-Akt pathway played a crucial role in CEFFE-induced acceleration of osteogenesis in ADSCs. The study confirms CEFFE's significant enhancement of ADSCs osteogenic potential and sheds light on the underlying mechanisms. These findings provide a preclinical foundation for potential applications in bone tissue engineering and regenerative medicine.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AIM2-Silenced Dendritic Cells Possess Immunosuppressive Phenotype and Prolong Allograft Survival by Modulating the Th1/Th17/Treg Balance","authors":"Qian Jian,&nbsp;Pengrui Cheng,&nbsp;Zongli Fu,&nbsp;Hanyu Wang,&nbsp;Hanyuan Zhang,&nbsp;Ronghai Deng,&nbsp;Yi Ma","doi":"10.1096/fj.202401860RRR","DOIUrl":"10.1096/fj.202401860RRR","url":null,"abstract":"<div>\u0000 \u0000 <p>Dendritic cells (DCs) serve a pivotal and diverse role in the modulation of transplant immunity, wherein alterations in their maturation state influence the balance between promoting immunotolerance and exacerbating inflammatory responses. Recent studies have revealed a spectrum of novel mechanisms through which absent in melanoma 2 (AIM2) regulates the functions of immune cells. However, the impact of AIM2 on the regulatory functions of dendritic cells in alloimmunity has not been thoroughly investigated. In this study, we constructed a recombinant adenovirus vector containing AIM2 interference sequences for the transduction of DCs, aiming to suppress AIM2 expression within these cells. Our findings indicate that silencing AIM2 preserved a semi-mature status of DCs upon lipopolysaccharide (LPS) exposure, alongside maintaining reduced levels of pro-inflammatory cytokine secretion and enhanced phagocytic activity. When co-cultured with allogeneic naive T cells, AIM2-silenced DCs demonstrated reduced activation potential of CD4⁺ and CD8⁺ T cells in response to LPS stimulation. The transfusion of AIM2-silenced DCs into recipient mice led to a notable prolongation of graft survival and a decrease in inflammatory cell infiltration within the graft. Furthermore, mice treated with AIM2-silenced DCs exhibited a higher percentage of regulatory T cells in their spleen and abdominal lymph nodes, concomitant with a decrease in the proportions of Th1 and Th17 cell subpopulations. AIM2-silenced DCs exhibit stable immunosuppressive capabilities, offering an effective strategy for alleviating allograft rejection.</p>\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}