Theranostics最新文献

{"title":"Single-shot multiparametric MRI for separating <i>T₂</i> effects from dynamic glucose-enhanced contrast.","authors":"Junxian Jin, Haizhen Ding, Zhekai Chen, Yuan Huang, Hongmin Chen, Zhong Chen, Lin Chen","doi":"10.7150/thno.116483","DOIUrl":"https://doi.org/10.7150/thno.116483","url":null,"abstract":"<p><p><b>Background:</b> Glucose is a central substrate in cellular metabolism and serves as a non-invasive biomarker for pathological processes. Dynamic glucose-enhanced (DGE) MRI based on chemical exchange saturation transfer (CEST) offers a promising tool for mapping glucose uptake, but its quantification is confounded by glucose-induced changes in <i>T₂</i> relaxation in addition to glucose concentration. <b>Methods:</b> We developed a single-shot multiparametric CEST (MP-CEST) MRI sequence based on multi-echo spatiotemporal encoding (SPEN), enabling the simultaneous acquisition of <i>T₂</i> and saturation-weighted proton density (PD) maps within a single scan. To correct for <i>T₂</i> -related confounding effects in glucoCEST quantification, a two-step correction strategy was employed. First, the saturation-weighted PD maps, which mitigate <i>T₂</i> -dependent signal attenuation during image acquisition, were used to reconstruct the Z-spectrum, thereby providing a more accurate representation of the true saturation signal amplitude. Second, calibration curves derived from Bloch-McConnell simulations were applied in combination with the simultaneously acquired <i>T₂</i> maps to compensate for spillover effects in the Z-spectrum, thereby improving glucose-specific CEST contrast. The full framework was validated through phantom experiments and <i>in vivo</i> studies in rat brain and tumor xenograft models. Quantitative performance was evaluated by computing the Pearson correlation between DGE signals and <i>T₂</i> values before and after correction, as well as by comparing fitted <i>T₂</i> and PD values with reference maps. <b>Results:</b> Phantom experiments demonstrated high accuracy in PD and <i>T₂</i> quantification (R² > 0.99). <i>In vivo</i> studies in rat brain and tumor xenografts showed that the proposed correction method significantly reduced the correlation between DGE signals and <i>T₂</i> values, improving the specificity of glucose-related contrast. In addition, <i>T₂</i> maps provided complementary structural and physiological information relevant to tumor heterogeneity and tissue microstructure. <b>Conclusions:</b> The proposed MP-CEST approach improves the robustness and accuracy of DGE quantification, offering a more comprehensive metabolic imaging framework applicable to both oncological and neurological research.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9678-9694"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213600","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}

{"title":"Biofilm-disrupting heterojunction microneedles: dual ROS amplification and glucose deprivation for accelerated diabetic wound healing.","authors":"Wenjie You, Feng Xiao, Zichao Cai, Jiaxin Zhao, Zhengyao Zhang, Weikang Hu, Yun Chen, Kwang Leong Choy, Zijian Wang","doi":"10.7150/thno.120787","DOIUrl":"https://doi.org/10.7150/thno.120787","url":null,"abstract":"<p><p><b>Rationale:</b> Diabetic wound healing process is critically hindered by bacterial infection, bacterial biofilm formation, and persistent hyperglycemia. Biomolecular microneedles represent a promising alternative to conventional therapies such as antibiotics and antibiotic-loaded wound dressings, owing to the advantages like reduced risk of drug resistance and enhanced long-term efficacy. However, the microneedles that fulfill the clinical needs of diabetic wounds have rarely been reported. <b>Methods:</b> A glucose oxidase (GOx)-laden Ti₃C₂/In₂O₃ (INTG) heterojunction was engineered as a nano-micro platform for reactive oxygen species (ROS) amplification and glucose deprivation, and subsequently immobilized onto the gelatin methacryloyl (GelMA) microneedle tips to obtain double-layer microneedles (GITG microneedles). Their physiochemical properties and biomedical applications were comprehensively investigated. <b>Results:</b> For INTG heterojunction, the formation of Schottky structure significantly improved the oxygen absorption capacity, facilitated the generation and migration of photogenerated electron-hole pairs, thereby promoting the ROS generation. Besides, under near-infrared (NIR) irradiation, GITG microneedles effectively inhibited bacterial proliferation and survival by generating ROS, thereby preventing the formation of bacterial biofilm. Additionally, GITG microneedles accelerated wound closure and facilitated skin tissue regeneration in a rat model through multiple mechanisms. <b>Conclusion:</b> This study developed an advanced microneedle platform enabling on-demand multimodal treatment, demonstrating significant potential for clinical diabetic wound management.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9757-9774"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213618","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}

{"title":"Dissecting Tertiary Lymphoid Structures in Cancer: Maturation, Localization and Density.","authors":"Guang-Liang Su, Meng-Jie Zhang, Hao Li, Zhi-Jun Sun","doi":"10.7150/thno.113940","DOIUrl":"https://doi.org/10.7150/thno.113940","url":null,"abstract":"<p><p>Tertiary lymphoid structures (TLSs) refer to ectopic lymphoid aggregates that form in non-lymphoid tissues at sites of chronic inflammation including cancers. TLSs have been recognized as significant predictors of the efficacy of immune checkpoint blockade (ICB) therapies and have the potential to elicit robust anti-tumor immune response. However, recent studies have revealed substantial heterogeneity in TLSs across different individuals and cancer types, which directly impacts the effectiveness of anti-tumor immunity. Concretely, the maturation status, localization, and density of TLSs profoundly influence the dynamic interactions among immune cells within these structures, potentially leading to adverse effects. This review provides an in-depth exploration of how the heterogeneity of TLSs influences cellular composition and immune dynamics, with the objective of influencing the efficacy of ICB therapies and modulating prognostic prediction accuracy. Additionally, the potential of combining TLSs with other biomarkers for predicting anti-tumor immunity outcomes is further investigated, alongside the introduction of advanced technologies for evaluating TLS heterogeneity. Collectively, these analyses aim to advance the understanding of TLS heterogeneity and facilitate its translation into clinical and translational medicine applications.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9459-9485"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213628","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}

{"title":"Integrative spatially resolved proteomic and metabolomic imaging reveals synovitis endotypes implicated in osteoarthritis progression.","authors":"Lin Zhu, Xin Diao, Chenrui Yuan, Chun Man Lawrence Lau, Jianing Wang, Wenlong Wu, Ali Mobasheri, Xavier Houard, Chunyi Wen, Zongwei Cai","doi":"10.7150/thno.117788","DOIUrl":"https://doi.org/10.7150/thno.117788","url":null,"abstract":"<p><p><b>Rationale</b>: Synovial fibrosis, driven by myofibroblast activation and extracellular matrix remodelling, is fundamental in osteoarthritis (OA) pathogenesis but remains poorly understood due to the spatial heterogeneity of synovial inflammation (synovitis). Accurate molecular endotyping of synovial inflammation is essential for effective treatment of OA given its multifactorial nature, yet it requires integrating multiple layers of information with spatial context due to the significant heterogeneity of the tissue. <b>Methods:</b> In this proof-of-concept study, we leveraged MALDI mass spectrometry imaging to achieve spatial metabolomic maps that complement high-content proteomic profiles. Microflow liquid chromatography was employed to improve the robustness and throughput of spatial proteomics. By coupling these spatially resolved datasets, we establish a pseudo time trajectory of heterogeneous synovitis in human knee OA using an integrative framework of spatially resolved proteomics and matrix-assisted laser desorption/ionization mass spectrometry imaging. <b>Results</b>: Clustering 3534 proteins and 79 energy metabolites from spatial proteomic and metabolomic image datasets reveals four distinct functional stages of OA synovitis, i.e., quiescent, microvasculopathic, pre-fibrotic, and post-fibrotic stages, which enables construction of a corresponding pseudo time. Network analyses elucidate the functional links among these stages, highlighting an immune-metabolic axis from endothelial injury and microvascular thrombosis toward myofibroblast activation. <b>Conclusions:</b> This integrative multi-omics imaging approach informs the inflammatory endotype of OA, supporting a vascular aetiology of synovial fibrosis and offering mechanistic insights that could inform more targeted therapeutic strategies. Validation in larger, stratified patient cohorts will be critical to refine our findings and accelerate their clinical usages.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9729-9741"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213733","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}

{"title":"Hot-spot empowered gold nanoparticles for theranostics in breast cancer.","authors":"Meng Tian, Shiqi Hu, Wen Sun, Ying Hu, Xingyi Ma","doi":"10.7150/thno.119678","DOIUrl":"https://doi.org/10.7150/thno.119678","url":null,"abstract":"<p><p>Breast cancer, being the most prevalent malignant tumor among women, confronts severe challenges in its early detection and precise treatment. Traditional diagnostic approaches have drawbacks in terms of sensitivity and specificity, and are invasive, thereby making it arduous to satisfy practical demands. Nanomedicine has introduced novel diagnostic and therapeutic modalities for breast cancer, particularly gold nanoparticles (AuNPs), which have been utilized on account of their distinctive optical and physicochemical attributes. Hot-spot empowered AuNPs have rapidly emerged and demonstrated significant potential in the diagnosis and treatment of breast cancer. From a technical standpoint, the design and synthesis of AuNPs hot-spot are constantly evolving, ranging from the control of number to the control of structure and efficient control of hot-spot utilizations, establishing a development model of \"number-structure-efficient utilization\". Hot-spot empowered AuNPs are extensively employed in diagnosis and therapy, facilitating targeted drug delivery, photothermal and photodynamic therapy, and multimodal integration therapy, and also achieving the function of theranostics in an innovative manner. We have deliberated on the challenges and future development prospects of precision medicine for the diagnosis of early breast cancer and individualized treatment.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9695-9728"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213701","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}

{"title":"Luminal Stem-like Cells in High-Risk/Locally Advanced Prostate Cancer Promote Resistance to Hormonal Therapy.","authors":"Guyu Tang, Jing Liu, Xiaomei Gao, Kai Yuan, Minfeng Chen, Long Wang, Lin Qi, Yi Cai","doi":"10.7150/thno.112496","DOIUrl":"https://doi.org/10.7150/thno.112496","url":null,"abstract":"<p><p><b>Introduction:</b> High-risk/locally advanced prostate cancer (HRLPC) accounts for a large proportion of prostate cancer cases in China and is associated with a high recurrence rate. Androgen deprivation therapy-based treatment offers limited benefits, which may be associated with changes in epithelial cells and the tumor microenvironment (TME) after treatment. However, the cellular composition and molecular characteristics of the subpopulations following hormonal treatment in HRLPC remain unclear. <b>Methods:</b> To investigate the molecular characteristics of residual tumor samples in HRLPC patients following hormonal therapy and to identify the reasons for their high recurrence rates, this study performed single-cell sequencing on nine HRLPC patients. Additionally, by establishing patient-derived organoids (PDOs) and conducting drug screening, we analyzed epithelial cell subpopulations at different treatment stages and explored potential therapeutic strategies. <b>Results:</b> This study identified a population of luminal stem-like epithelial cells (Lum stem-like) with high transcriptional activity of SOX9. After hormonal therapy, these cells were still alive and became the predominant component of epithelial luminal cells. Additionally, after hormonal therapy, the proportion of stromal components, such as fibroblasts and endothelial cells, significantly increased in the TME, and the intercellular communication between fibroblasts and other cells was enhanced. The level of immune infiltration decreased, but the proportion of FOXP3⁺ Treg cells increased, leading to an \"exhausted\" immune microenvironment state. We confirmed that PDOs can accurately reflect the epithelial subtypes of the primary tumor, such as Lum stem-like cells. Using 18 potential therapeutic agents at the organoid level for drug screening, the results showed that the Lum stem-like cells exhibited greater sensitivity to platinum-based drugs. <b>Conclusions:</b> This study identified the dominant Lum stem-like epithelial cell subpopulation, along with changes in the TME characterized by increased stroma and decreased immune infiltration after hormonal therapy in HRLPC. These findings can help guide the subsequent treatment strategies for HRLPC patients.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9558-9579"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213712","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}

{"title":"Advances and challenges in decellularized adipose tissue based composite hydrogels for adipose tissue regeneration: a review over the last fifteen years.","authors":"Lu Cui, Tian-Jie Lyu, Bin Fu, Yubo Wang, Qing Qu, Fanglin Wang, Rui Guo, Jun Fan","doi":"10.7150/thno.120300","DOIUrl":"https://doi.org/10.7150/thno.120300","url":null,"abstract":"<p><p>Adipose tissue regeneration has emerged as a transformative strategy for addressing soft-tissue defects resulting from trauma, oncologic resection, and burn injuries, leveraging adipose tissue's dual role as a dynamic endocrine organ that regulates systemic metabolism. Decellularized adipose tissue (DAT) scaffolds hold significant promise in adipose tissue regeneration due to their unique preservation of pro-adipogenic and structurally preserved extracellular matrix (ECM) components. However, their clinical translation faces bottlenecks, including inadequate compressive modulus, unpredictable biodegradation kinetics and limited neovascularization capacity. This review critically synthesizes methodological advancements in DAT processing, systematically evaluating protocol efficacy in DAT preservation versus immunogenic residue elimination while assessing their translational potential as implant materials. Building upon methodological innovations in DAT composite hydrogel engineering since 2013, this overview concurrently elucidates mechanobiological regulation paradigms governing hydrogel functionality and evaluates crosslinking strategies that optimize structural fidelity. Critical challenges and emerging frontiers are also discussed. The current comparative assessment of material performance metrics may offer new insights for further investigation and translational optimization in DAT based composite hydrogels for repair of soft tissue defects.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9508-9532"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213622","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}

{"title":"Engineering a spleen-selective mRNA-LNPs vaccine by decoupling the inflammation from cellular immunity-mediated cancer immunotherapy.","authors":"Xiaoke Gao, Meng Zhang, Shiyang Du, Lixia Ma, Xiaohan Yao, Boao Xie, Jiajia Wan, Yuqiao Sheng, Bo Qin, Wenjing Deng, Ningjing Lei, Wentao Mo, Ming Wang, Zhijun Sun, Zhihai Qin, Fazhan Wang","doi":"10.7150/thno.118976","DOIUrl":"https://doi.org/10.7150/thno.118976","url":null,"abstract":"<p><p><b>Rationale:</b> mRNA vaccine-based cancer immunotherapy requires innate immune activation followed by potent cellular immunity. Vectors of lipid nanoparticles (LNPs) with proinflammatory properties activate the innate immune pathway, while excessive inflammatory response of mRNA-LNPs vaccine often results in systemic inflammation, compromising its therapeutic safety. <b>Methods:</b> Here, we engineered a spleen-selective mRNA-LNPs (mRNA-sLNPs) vaccine by decoupling the excessive inflammation from strong cellular immunity through ionizable lipids substituting for potent cancer immunotherapy. <b>Results:</b> The mRNA-sLNPs vaccine with reduced inflammation achieved superior mRNA translation in the spleen and enhanced antigen-specific cellular immune responses. Mechanistically, the optimized mRNA-sLNPs vaccine amplified lysosomal escape and boosted antigen presentation with moderate co-stimulatory molecule expression by mitigating TLR4/MyD88/NF-κB signaling and pro-inflammatory cytokine secretion. In therapeutic mouse models, the engineered mRNA vaccine significantly inhibited both the growth of subcutaneous B16F10-OVA melanomas and the development of lung metastases following intravenous injection of B16F10-OVA cells with augmented infiltration of CD4⁺ and CD8⁺ T cells in the tumor microenvironment. <b>Conclusion:</b> Our findings might redefine the design principles of mRNA-LNPs vaccine as diminishing the inflammation of LNPs does not compromise cellular immunity, offering a clinically translatable strategy to advance mRNA vaccines for cancer immunotherapy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9643-9662"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213732","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}

{"title":"Synthetic reprogramming of tumor cell fate for modulating radiotherapy-induced dynamic responses: perspectives on radiosensitizing and immunoregulatory effects.","authors":"Wei Zhou, Lulu Wang, Hui Zhang, Yongzhong Wu, Menghuan Li, Zhong Luo","doi":"10.7150/thno.119822","DOIUrl":"https://doi.org/10.7150/thno.119822","url":null,"abstract":"<p><p>Radiotherapy is one of the most commonly prescribed anticancer modalities in the clinic, which is widely recognized as an effective and safe treatment for a broad spectrum of solid tumor indications. Interestingly, there is increasing evidence that the tumors can dynamically modulate cell fate decisions after ionizing radiation (IR) exposure, which is beneficial for escaping the radiation-induced antitumorigenic cell damaging and immunostimulatory impacts. Consequently, the regulatory network of cell fate determination could be a promising target for enhancing the susceptibility of tumor cells to various radiotherapeutic modalities. In this review, we provide a comprehensive account on the mechanisms of post-radiation cell fate control in tumor cells to escape programmed cell death (PCD) including apoptosis, necrosis, pyroptosis and ferroptosis, while special emphasis is placed on the development of synthetic agents for the therapeutic modulation of post-radiation tumor cell fate decisions to facilitate tumor cell eradication, focusing on their therapeutic utility for amplifying the RT-induced direct tumor cell damage as well as promoting the post-IR antitumor immunity. We envision that these synthetic cell fate regulatory technologies could provide new avenues for improving radiotherapeutic efficacy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9533-9557"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213597","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}

{"title":"Macrophage-TREM2 promotes cardiac repair by restricting the infiltration of CD8⁺ T cells via CXCL16-CXCR6 axis after myocardial infarction.","authors":"Linlin Zhang, Sheng Wang, Yu Ding, Tao Zheng, Jie Sheng, Yanshan Chen, Zhiyue Wang, Ximei Dai, Canbiao Wang, Long Ma, Jing Pan, Yunming Zhang, Longjiang Zhang","doi":"10.7150/thno.118014","DOIUrl":"https://doi.org/10.7150/thno.118014","url":null,"abstract":"<p><p><b>Background:</b> Infiltrated CD8⁺ T cells following myocardial infarction (MI) are potential myocardial injury factors, triggering autoimmunity by binding to myocardial cell-specific proteins. It has been reported that autoimmunity after MI is restricted during the fibrosis period. Nevertheless, the relevant mechanisms of this process have scarcely been explored. Cell-cell communication analysis suggests that macrophages are the most promising group for restricting T cell activity. Unbiased single-cell sequencing data screening indicates that TREM2 is a leading gene significantly upregulated after MI. However, how TREM2 restricts the activity of CD8⁺ T cells remains unknown. <b>Methods and Results:</b> The adoptive transfer of circulating CD8⁺ T cells after MI proved their autoimmune attribute of attacking cardiomyocytes. CD8 antagonistic antibodies and the anti-autoimmune drug Ozanimod effectively inhibited the infiltration of CD8⁺ T cells and significantly ameliorated the damage to cardiomyocytes after MI. In TREM2 KO mice, the infiltration of CD8⁺ T cells in the myocardium was significantly increased without influencing the number of Treg cells. The results of cell-cell communication revealed that CXCL16-CXCR6 was the most predominant receptor-ligand pair between macrophages and CD8⁺ T cells. The results of ELISA and Transwell indicated that TREM2 deficiency led to an increase in CXCL16 secretion, thereby enhancing the chemotaxis of CD8⁺ T cells. The KEGG analysis and Western Blot results demonstrated that the deficiency of TREM2 augmented the activation of the PI3K-AKT signaling pathway, thereby resulting in an increase in CXCL16 secretion. Moreover, TREM2 deficiency also reduced VEGFC secretion and cardiac lymphangiogenesis, thereby leading to the impairment of immune cell drainage. Additionally, TREM2 deficiency reversed Ozanimod's effect on inhibiting CD8⁺ T cell infiltration. The overexpression of TREM2 significantly decreased CD8⁺ T cell infiltration and improved cardiac function. <b>Conclusions:</b> Macrophage TREM2 promotes cardiac repair by limiting the infiltration of CD8⁺ T cells and facilitating lymphangiogenesis.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 18","pages":"9580-9600"},"PeriodicalIF":13.3,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213702","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}