American Journal of Transplantation最新文献_第10页

Comment on "There is nothing equitable about a wasted organ; eliminating out-of-sequence allocation for 30 days decreases utilization of hard-to-place kidneys". 评论“被浪费的器官没有什么公平可言；取消30天的无序分配减少了难以安置的肾脏的利用率。”

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-18 DOI: 10.1016/j.ajt.2026.08.010

Zachary Joseph, Miko Yu, Jesse Schold, Sumit Mohan

引用次数: 0

A hepatocyte circular RNA derived from FADS2 exons 2 to 5-heterogeneous nuclear ribonucleoprotein D-purinergic receptor P2Y, subtype 1 axis restrains arachidonic acid output and tunes alloimmune injury in pediatric liver transplantation. 肝细胞circFADS2-HNRNPD-P2RY1轴抑制花生四烯酸输出并调节儿童肝移植的同种免疫损伤。

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-18 DOI: 10.1016/j.ajt.2026.07.036

Qi Pan, Aiwei Zhou, Tianyi Yang, Tianyi Lin, Bingran Wang, Wanglong Xiao, Yunmu Gao, Jiaqi Song, Hongyuan Liu, Wanmei Zhou, Zitong Chen, Yingchun Yang, Qianxiao Cheng, Zhicong Zhao, Taihua Yang, Yuan Liu, Yongbo Liu, Qiang Xia

{"title":"A hepatocyte circular RNA derived from FADS2 exons 2 to 5-heterogeneous nuclear ribonucleoprotein D-purinergic receptor P2Y, subtype 1 axis restrains arachidonic acid output and tunes alloimmune injury in pediatric liver transplantation.","authors":"Qi Pan, Aiwei Zhou, Tianyi Yang, Tianyi Lin, Bingran Wang, Wanglong Xiao, Yunmu Gao, Jiaqi Song, Hongyuan Liu, Wanmei Zhou, Zitong Chen, Yingchun Yang, Qianxiao Cheng, Zhicong Zhao, Taihua Yang, Yuan Liu, Yongbo Liu, Qiang Xia","doi":"10.1016/j.ajt.2026.07.036","DOIUrl":"10.1016/j.ajt.2026.07.036","url":null,"abstract":"Pediatric liver transplantation is frequently complicated by T cell-mediated rejection (TCMR), yet graft-intrinsic regulators and actionable biomarkers remain limited. Using integrative RNA profiling and mechanistic interrogation, we identified circular RNA derived from fatty acid desaturase 2 (FADS2) exons 2 to 5 (circFADS2) as a hepatocyte-dominant circular RNA that is markedly reduced in TCMR. circFADS2 distinguishes TCMR from nonrejection with an area under the curve value of 0.86, supporting its potential as a candidate biopsy-based molecular adjunct to characterize rejection-associated graft remodeling. Mechanistically, circFADS2 binds purinergic receptor P2Y, subtype 1 (P2RY1) messenger RNA and engages a heterogeneous nuclear ribonucleoprotein D-dependent decay program to promote transcript destabilization, reducing P2RY1 abundance and attenuating P2RY1-linked signaling output as assessed by diminished agonist-evoked Ca2+ mobilization and reduced phosphorylation of downstream effectors, including MAP kinase-interacting serine/threonine-protein kinase 1 and cytosolic phospholipase A2. Consistent with this signaling attenuation, circFADS2 overexpression reduces arachidonic acid (AA) and AA-derived lipid mediators released from hepatocytes. Limiting AA is accompanied by reduced CD4+ T cell activation, proliferation, and effector cytokine production in hepatocyte-conditioned media assays. Finally, pharmacologic P2RY1 stimulation exacerbates, whereas P2RY1 inhibition alleviates, graft injury in a murine liver transplantation model, supporting the in vivo relevance of the P2RY1-linked pathway downstream of circFADS2.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786066","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}

引用次数: 0

Banff Liver Allograft Pathology Group: late rejection activity is insufficiently represented in the current diagnostic framework - rationale and goals for revision. 班夫同种异体肝移植病理组：晚期排斥反应在目前的诊断框架中没有充分体现——修订的理由和目标。

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-14 DOI: 10.1016/j.ajt.2026.08.004

Christopher Bellamy, Claudia Mescoli, Khashayar Asadi, Oyedele A Adeyi, Rachel M Brown, Lindsey Clarke, Zeynep Demir, Sadhna Dhingra, Michail Doukas, Mohamad El Hag, Bastian Engel, Sandy Feng, Maria I Fiel, Alessandro Gambella, Krzyztof Grzyb, Horonori Haga, Laura Heij, Elmar Jaekel, Anthea Lafreniere, Jan P Lerut, Andrew Lesniak, Geoffrey W McCaughan, Catriona McKenzie, Rosa Miquel, Charlotte Mussini, Deslie Neil, Anna L Paterson, Avandi A Pendse, Henrik M Reims, Olorunda Rotimi, Alberto Sanchez Fueyo, Thomas D Schiano, Mylene Sebagh, Maxwell Smith, Heather L Stevenson, Timucin Taner, Ryan Y Tanigawa, Richard Taubert, Elena Y Uebayashi, Funda Yilmaz, Jacqueline G O'Leary, Anthony J Demetris

{"title":"Banff Liver Allograft Pathology Group: late rejection activity is insufficiently represented in the current diagnostic framework - rationale and goals for revision.","authors":"Christopher Bellamy, Claudia Mescoli, Khashayar Asadi, Oyedele A Adeyi, Rachel M Brown, Lindsey Clarke, Zeynep Demir, Sadhna Dhingra, Michail Doukas, Mohamad El Hag, Bastian Engel, Sandy Feng, Maria I Fiel, Alessandro Gambella, Krzyztof Grzyb, Horonori Haga, Laura Heij, Elmar Jaekel, Anthea Lafreniere, Jan P Lerut, Andrew Lesniak, Geoffrey W McCaughan, Catriona McKenzie, Rosa Miquel, Charlotte Mussini, Deslie Neil, Anna L Paterson, Avandi A Pendse, Henrik M Reims, Olorunda Rotimi, Alberto Sanchez Fueyo, Thomas D Schiano, Mylene Sebagh, Maxwell Smith, Heather L Stevenson, Timucin Taner, Ryan Y Tanigawa, Richard Taubert, Elena Y Uebayashi, Funda Yilmaz, Jacqueline G O'Leary, Anthony J Demetris","doi":"10.1016/j.ajt.2026.08.004","DOIUrl":"https://doi.org/10.1016/j.ajt.2026.08.004","url":null,"abstract":"Late liver allograft rejection is under-recognized because it is often clinically silent, liver tests are insensitive, protocol biopsies are uncommon, and the histology differs from classic early acute T cell-mediated rejection (TCMR) manifesting in the initial weeks after transplantation. Differences in tempo and pathogenesis lead to distinct clinical and histologic manifestations. Late- compared with acute-TCMR is characterized by more prevalent interface and perivenular inflammatory activity, a lymphocyte-predominant infiltrate and fibrosis, with less conspicuous portal duct-centered and subendothelial venular inflammation. The traditional Banff RAI scheme that works consistently well to diagnose acute-TCMR is less well calibrated to account for these later shifts of inflammatory target and density, risking under-diagnosis of clinically significant late-TCMR. This document lays out the histopathologic characteristics of acute- vs. late-TCMR and the rationale for updating the Banff scoring system for liver allograft rejection to better incorporate currently unrepresented histology features correlating with a molecular rejection signature into the Banff rejection scheme.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756993","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}

引用次数: 0

The early posttransplant lung microbiome and IP10/CXCL10 are associated with chronic lung allograft dysfunction: A prospective study with 5-year follow-up. 移植后早期肺微生物组和CXCL10与慢性同种异体肺移植功能障碍相关：一项5年随访的前瞻性研究

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-14 DOI: 10.1016/j.ajt.2026.08.009

Carter Merenstein, John E McGinniss, Robert Gallop, Samantha A Whiteside, Krishna Pandya, Michelle Oyster, Jevon Graham-Wooten, Laurel Kalman, Emily Clausen, Edward Cantu, Joshua M Diamond, Frederic D Bushman, Jason D Christie, Ronald G Collman

{"title":"The early posttransplant lung microbiome and IP10/CXCL10 are associated with chronic lung allograft dysfunction: A prospective study with 5-year follow-up.","authors":"Carter Merenstein, John E McGinniss, Robert Gallop, Samantha A Whiteside, Krishna Pandya, Michelle Oyster, Jevon Graham-Wooten, Laurel Kalman, Emily Clausen, Edward Cantu, Joshua M Diamond, Frederic D Bushman, Jason D Christie, Ronald G Collman","doi":"10.1016/j.ajt.2026.08.009","DOIUrl":"10.1016/j.ajt.2026.08.009","url":null,"abstract":"Chronic lung allograft dysfunction (CLAD) is a major barrier to long-term lung transplantation success. Microbial factors have been linked to CLAD risk, and sequence-based methods have been applied recently to identify potential microbial drivers, although patient heterogeneity and follow-up time have been limitations. We undertook a longitudinal cohort study of 186 patients transplanted for diseases other than cystic fibrosis. Dense lung sampling was carried out over the first year, and patients were followed for a median of 6.04 years. Bronchoalveolar lavage was analyzed by bacterial 16S ribosomal RNA gene sequencing and quantification. Postimplant bronchoalveolar lavage was assayed for cytokines and underwent metabolomics analysis. Seventy patients (38%) developed CLAD. CLAD development and shorter time to CLAD were associated with higher lung bacterial burden, particularly 6 months posttransplant, low Streptococcus/Prevotella ratio in lung 6 weeks posttransplant, and elevated lung IP10/CXCL10 immediately after implantation. Each factor was associated with distinct timing of CLAD onset. These factors, together with previously recognized clinical features, stratified patients into groups differing by >3-fold CLAD risk. Thus, increased lung bacteria and altered composition during the first year posttransplant and of IP10/CXCL10 immediately after implantation are associated with CLAD after transplantation for non-cystic fibrosis lung disease. Early events in the allograft may establish conditions affecting later graft failure, identify potentially modifiable mechanisms of injury, and provide biomarkers for CLAD risk.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756752","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}

引用次数: 0

Comment on "Beyond theory and into practice: A qualitative study of the experiences of xenotransplant recipients". 对“超越理论进入实践：异种移植受者经验的定性研究”的评论。

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-14 DOI: 10.1016/j.ajt.2026.08.008

Johannes Kögel

引用次数: 0

A preventable lung loss? The critical importance of technical adherence during thoracoabdominal normothermic regional perfusion. 可预防的肺损失？技术依附性在TA-NRP中的关键重要性。

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-13 DOI: 10.1016/j.ajt.2026.08.007

Mark Petrovic, Enock Adjei, Matthew Bacchetta, Konrad Hoetzenecker

引用次数: 0

Polygenic prediction of actinic keratosis identifies transplant recipients at risk of extreme lesion burden. 光化性角化病的多基因预测确定移植受者有严重病变负担的风险。

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-13 DOI: 10.1016/j.ajt.2026.08.006

Abishna Parasuraman, Rawaa Eltayib, Nirmala Pandeya, Catherine M Olsen, Matthew H Law, David C Whiteman, Stuart MacGregor, Mathias Seviiri

{"title":"Polygenic prediction of actinic keratosis identifies transplant recipients at risk of extreme lesion burden.","authors":"Abishna Parasuraman, Rawaa Eltayib, Nirmala Pandeya, Catherine M Olsen, Matthew H Law, David C Whiteman, Stuart MacGregor, Mathias Seviiri","doi":"10.1016/j.ajt.2026.08.006","DOIUrl":"10.1016/j.ajt.2026.08.006","url":null,"abstract":"Transplant recipients have an elevated risk of actinic keratosis (AK), a precursor of squamous cell carcinoma. We assessed whether an AK polygenic risk score (PRS) can identify transplant-naive individuals and transplant recipients at risk of multiple AKs who may benefit from early prevention. Using genome-wide association data (140 339 cases; 1 430 776 controls), we developed an AK PRS and evaluated it in cohort studies of European descent individuals in the QSkin Sun and Health Study (QSkin) (N = 12 843), Skin Tumors in Allograft Recipients Study (STAR) (N = 357), UK Biobank (N = 963), and All of Us (N = 1859). The PRS was strongly associated with higher AK burden in transplant-naive individuals, conferring a 5-fold increased risk of developing ≥20 AKs (odds ratio [OR] per standard deviation [SD] increase in the PRS = 5.06, 95% confidence interval [CI] = 4.69-5.46). In transplant recipients, it was associated with up to a 2.5-fold increased risk of developing ≥1 AK (United Kingdom Biobank [UKB] OR per SD = 2.49, 95% CI = 1.91-3.23; STAR OR per SD = 1.79, 95% CI = 1.10-2.91; All of Us OR per SD = 1.52, 95% CI = 1.35-1.70). The PRS improved prediction of ≥20 AKs by 13% beyond age and sex (AUC 0.90 vs 0.77) and identified the highest-risk 20% with a 9-fold increased risk in transplant-naive individuals (OR = 8.61, 95% CI = 7.26-10.22) and a 2-fold increased risk in transplant recipients (OR = 2.23, 95% CI = 1.26-4.20), compared to the middle-risk 60%. Incorporating PRS into pretransplant and posttransplant care could enable earlier, personalized prevention.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756925","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}

引用次数: 0

Systemic mitochondrial DNA kinetics after controlled donation after circulatory determination of death lung transplantation do not reflect donor warm ischemic injury: DACMEDAMPs, a prospective multicenter translational study. cDCD肺移植后的全身线粒体DNA动力学不反映供体热缺血损伤：dacmedamp，一项前瞻性多中心转化研究。

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-13 DOI: 10.1016/j.ajt.2026.08.005

Irene Bello, Ramon Martí, Aroa Gómez-Brey, Silvana Crowley Carrasco, Maria Jesús Melià, Elena García-Arumí, Javier Pérez Vélez, Maria Deu, Sara Naranjo, Eva Fieira, Marina Pérez-Redondo, Victor Mora, Maria Ángeles Ballesteros, Fernando Mosteiro, Elisabeth Coll, Beatriz Dominguez-Gil, Alberto Sandiumenge

{"title":"Systemic mitochondrial DNA kinetics after controlled donation after circulatory determination of death lung transplantation do not reflect donor warm ischemic injury: DACMEDAMPs, a prospective multicenter translational study.","authors":"Irene Bello, Ramon Martí, Aroa Gómez-Brey, Silvana Crowley Carrasco, Maria Jesús Melià, Elena García-Arumí, Javier Pérez Vélez, Maria Deu, Sara Naranjo, Eva Fieira, Marina Pérez-Redondo, Victor Mora, Maria Ángeles Ballesteros, Fernando Mosteiro, Elisabeth Coll, Beatriz Dominguez-Gil, Alberto Sandiumenge","doi":"10.1016/j.ajt.2026.08.005","DOIUrl":"10.1016/j.ajt.2026.08.005","url":null,"abstract":"Controlled donation after circulatory determination of death has markedly expanded the lung donor pool; however, the biological consequences of donor warm ischemia on mitochondrial injury and systemic danger signaling remain uncertain. Cell-free mitochondrial DNA (cf-mtDNA) has been implicated in ischemia-reperfusion injury, yet its systemic behavior in ventilated human lungs is incompletely characterized. We conducted a prospective, multicenter observational study in matched adult lung transplant recipients from controlled donation after circulatory determination of death and donation after brain death to characterize donor and recipient plasma cf-mtDNA kinetics and evaluate their relationship with warm ischemic exposure. Serial plasma samples were obtained from donors and from recipients. Donor plasma cf-mtDNA levels were comparable between groups. A divergence emerged at 72 hours after transplantation, reflected by a significant donor type-by-time interaction in adjusted longitudinal analysis. Neither total nor functional warm ischemia time was associated with cf-mtDNA concentrations. In multivariable analysis restricted to 72 hours, donor type was not independently associated with absolute systemic cf-mtDNA levels. Exploratory analysis of donor-derived cf-mtDNA demonstrated a decline in graft-derived mitochondrial DNA between reperfusion and 72 hours despite a concurrent increase in total cf-mtDNA. These findings suggest that posttransplant systemic cf-mtDNA dynamics reflect recipient-driven inflammatory processes rather than a direct surrogate of donor warm ischemic injury.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756859","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}

引用次数: 0

Marginal zone B cell targeting limits alloantigen availability to follicular dendritic cells and mitigates antibody-mediated rejection. 边缘区B细胞靶向限制同种抗原对滤泡树突状细胞的可用性并减轻抗体介导的排斥反应。

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-11 DOI: 10.1016/j.ajt.2026.08.002

Rodrigo B Gassen, Kaifeng Liu, Yoshikazu Ganchiku, Karina Lima, Ayman Al Jurdi, Katalin Susztak, Ciara N Magee, Naoka Murakami, Ivy A Rosales, Thiago J Borges, Leonardo V Riella

{"title":"Marginal zone B cell targeting limits alloantigen availability to follicular dendritic cells and mitigates antibody-mediated rejection.","authors":"Rodrigo B Gassen, Kaifeng Liu, Yoshikazu Ganchiku, Karina Lima, Ayman Al Jurdi, Katalin Susztak, Ciara N Magee, Naoka Murakami, Ivy A Rosales, Thiago J Borges, Leonardo V Riella","doi":"10.1016/j.ajt.2026.08.002","DOIUrl":"10.1016/j.ajt.2026.08.002","url":null,"abstract":"Chronic antibody-mediated rejection is a leading cause of allograft loss, with limited therapies that effectively target humoral immunity. Current immunosuppressive regimens primarily target T cells, leaving a critical gap in strategies to suppress antibody-driven rejection. Marginal zone (MZ) B cells are innate-like cells that can rapidly generate antibodies, but their role in donor-specific antibody generation and chronic rejection remains unclear. We developed novel murine models of chronic antibody-mediated rejection using HLA-A2 transgenic heart and kidney transplants that recapitulate clinical features of human disease. Using an anti-Notch2 antibody to selectively target MZ B cells, we observed reduced antigen-specific humoral responses, including decreases in germinal center B cells, plasma cells, donor-specific antibodies, and C4d deposition, alongside improved graft structure and function. Mechanistically, the reduction of MZ B cells disrupted antigen shuttling to follicular dendritic cells, leading to decreased follicular dendritic cell-associated alloantigen clusters and impaired germinal center reactions. These findings establish MZ B cells as key drivers of alloantibody formation and highlight Notch2 as a promising therapeutic target.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710850","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}

引用次数: 0

Enhancing stability and function of induced regulatory T cells through membrane-anchored transforming growth factor-β1 and interleukin-10 secretion to protect against graft-vs-host disease. 通过膜锚定的转化生长因子-β1和白细胞介素-10分泌增强诱导调节性T细胞的稳定性和功能，以防止移植物抗宿主病。

IF 8.1 2区医学

American Journal of Transplantation Pub Date : 2026-08-11 DOI: 10.1016/j.ajt.2026.08.003

Shuo Zhang, Ang Li, Xiangrong Li, Sen Li, Xiang Ji, Cuisong Zhu, Chenli Qiu, Xiaoyan Zhang, Jianqing Xu, Shuye Zhang

{"title":"Enhancing stability and function of induced regulatory T cells through membrane-anchored transforming growth factor-β1 and interleukin-10 secretion to protect against graft-vs-host disease.","authors":"Shuo Zhang, Ang Li, Xiangrong Li, Sen Li, Xiang Ji, Cuisong Zhu, Chenli Qiu, Xiaoyan Zhang, Jianqing Xu, Shuye Zhang","doi":"10.1016/j.ajt.2026.08.003","DOIUrl":"10.1016/j.ajt.2026.08.003","url":null,"abstract":"Graft-vs-host disease (GvHD) remains a key challenge in allogeneic transplantation, underscoring the need for effective therapies to establish immune tolerance. Adoptive regulatory T cell (Treg) therapy shows promise but is restricted by the limited expansion of natural Tregs (nTregs) and the instability of induced Tregs (iTregs). The latter are prone to losing forkhead box protein 3 expression and suppressive function in inflammatory microenvironments. Here, we developed membrane-anchored transforming growth factor-β1 (MAT) and interleukin (IL)-10 (IL-10)-secreting iTregs (MAT-iTregs), a novel engineered iTreg platform designed to enhance lineage stability and suppressive potency. MAT-iTregs express membrane-anchored transforming growth factor-β1 and produce high levels of interleukin-10 to amplify immunosuppression and maintain functional stability. We optimized construct design and manufacturing processes to yield highly enriched MAT-iTregs. In preclinical studies, MAT-iTregs outperformed conventional iTregs in safety profiles and therapeutic efficacy. MAT-iTregs significantly prolonged survival, reduced tissue injury, and attenuated pathogenic effector T cell responses in xenogeneic GvHD mice. Notably, MAT-iTregs maintained suppressive function, durable persistence, and a favorable safety profile in mouse models, with no evidence of converting to effector T cells and minimal tissue toxicity. Together, these findings support MAT-iTregs as a clinically translatable cell therapy to promote transplant tolerance and improve outcomes in GvHD.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710866","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}

引用次数: 0