JCI insight最新文献_第10页

Mutation-resolved single-cell transcriptomics reveals enhanced β-amyloid clearance in TET2-mutant human monocytes. 突变解决的单细胞转录组学显示tet2突变的人单核细胞中β-淀粉样蛋白清除增强。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.208804

Xiao Yang, Sameen Fatima, Salvador Sampere-Birlanga, Akshay Ware, Mariana Shumliakivska, Lukas Zanders, Srisurekha Radhakrishnan, Guillermo Luxán, David John, Stefan Günther, Silvia Mas-Peiro, Stefanie Dimmeler, Andreas M Zeiher, Wesley T Abplanalp

引用次数: 0

ATF7 drives diabetic wound healing via NOTCH1 repression and N1ICD-dependent macrophage polarization control. ATF7通过NOTCH1抑制和n1icd依赖性巨噬细胞极化控制驱动糖尿病伤口愈合。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.201178

Pengcheng Xu, Yuan Xue, Linlin Feng, Jingwen Kuang, Xiaochen Hu, Huiyi Tang, Biao Cheng, Limin Wei

{"title":"ATF7 drives diabetic wound healing via NOTCH1 repression and N1ICD-dependent macrophage polarization control.","authors":"Pengcheng Xu, Yuan Xue, Linlin Feng, Jingwen Kuang, Xiaochen Hu, Huiyi Tang, Biao Cheng, Limin Wei","doi":"10.1172/jci.insight.201178","DOIUrl":"10.1172/jci.insight.201178","url":null,"abstract":"Chronic, non-healing wounds are a severe diabetic complication. The underlying mechanisms are not fully understood, and the role of ATF7 in this context has not been well characterized. In our study, we utilized db/db diabetic mice and AAV-mediated keratinocyte-specific Atf7 overexpression in vivo. HaCaT keratinocyte/THP-1 macrophage cocultures under high glucose were used in vitro. Our results showed that ATF7 was upregulated in diabetic wounds. Keratinocyte-specific Atf7 overexpression accelerated diabetic wound closure, enhanced re-epithelialization, granulation tissue formation, and keratinocyte proliferation, while suppressing macrophage M1 polarization and inflammation. Multiomics screening identified NOTCH1 as a key ATF7 target. ATF7 transcriptionally repressed NOTCH1 by recruiting Suv39h1, increasing H3K9me3 at the NOTCH1 promoter. This reduced NOTCH1 protein and its active intracellular domain (N1ICD) within keratinocyte-derived exosomes. ATF7-overexpressing keratinocyte exosomes carried less N1ICD, leading to decreased N1ICD transfer to macrophages and subsequent inhibition of M1 polarization. Notably, local injection of exosomes from ATF7-overexpressing keratinocytes accelerated wound healing in db/db mice. In summary, ATF7 promotes diabetic wound healing by repressing NOTCH1 transcription via H3K9me3, thereby reducing exosomal N1ICD secretion from keratinocytes and inhibiting macrophage M1 polarization. This identifies the ATF7/NOTCH1/exosome axis as a therapeutic target.","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"11 16","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808618","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}

引用次数: 0

Clonal hematopoiesis is associated with progression of idiopathic pulmonary fibrosis. 克隆造血与特发性肺纤维化的进展相关。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.198458

Lori Asarian, Jianlong Jia, Dmytro Sirokha, Lara Paulini, Daniela Dietel, Mircea Gabriel Stoleriu, Marion Frankenberger, Ali Önder Yildirim, Katharina S Götze, Juergen Behr, Gary M Hunninghake, Isis E Fernandez

引用次数: 0

Innate immune sensor NOD2 promotes cartilage degradation and osteoarthritis progression by stabilizing TRAF6 in chondrocytes. 先天免疫传感器NOD2通过稳定软骨细胞中的TRAF6促进软骨降解和骨关节炎进展。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.196750

Yuting Wang, Song Li, Yonghui Dong, Jiaming Zhang, Jian Liu, Zhenggang Wang, Shuang Liang, Nathan R Martinez, Hongxu Pu, Peng Cheng, Anmin Chen, Qing Yang, Charles Kf Chan, Wen Jiang, Jun Xiao, Fengjing Guo, Liming Zhao

{"title":"Innate immune sensor NOD2 promotes cartilage degradation and osteoarthritis progression by stabilizing TRAF6 in chondrocytes.","authors":"Yuting Wang, Song Li, Yonghui Dong, Jiaming Zhang, Jian Liu, Zhenggang Wang, Shuang Liang, Nathan R Martinez, Hongxu Pu, Peng Cheng, Anmin Chen, Qing Yang, Charles Kf Chan, Wen Jiang, Jun Xiao, Fengjing Guo, Liming Zhao","doi":"10.1172/jci.insight.196750","DOIUrl":"10.1172/jci.insight.196750","url":null,"abstract":"Inflammation driven by the innate immune response plays a crucial role in osteoarthritis (OA) pathogenesis, yet the underlying mechanisms remain incompletely understood. Moreover, current antiinflammatory therapies primarily offer symptomatic relief without altering disease progression. Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that detects a broad range of microbial and damage-associated stimuli and has been implicated in several inflammatory conditions. In this study, we investigated the role of NOD2 in OA-associated inflammation and cartilage degradation. Elevated NOD2 expression was observed in both human and mouse osteoarthritic cartilage. Conditional KO of Nod2 in chondrocytes suppressed inflammation-induced catabolic responses in vitro and protected against cartilage degradation in mouse OA models. Mechanistically, we identified tumor necrosis factor receptor-associated factor 6 (TRAF6) as a key downstream mediator through which NOD2 promotes chondrocyte catabolism. Furthermore, we showed that pharmacological inhibition of NOD2 using 2 independent small-molecule inhibitors significantly attenuated OA progression in vivo. Collectively, these findings establish NOD2 as a critical regulator of OA-associated inflammation and cartilage degradation, and they highlight its potential as a therapeutic target for disease-modifying OA treatment.","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"11 16","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808578","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}

引用次数: 0

Platelet-derived S100A9 contributes to endotheliopathy in alcohol-associated hepatitis. 血小板来源的S100A9有助于酒精相关性肝炎的内皮病变。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.201114

Fallyn Kirlin, Nima Fattahi, Rolando Garcia-Milian, Florine Collin, Weiwei Wang, Yohan Kim, Fabrice Lucien, Zhaoli Sun, TuKiet T Lam, John Hwa, Yasuko Iwakiri, Matthew J McConnell

{"title":"Platelet-derived S100A9 contributes to endotheliopathy in alcohol-associated hepatitis.","authors":"Fallyn Kirlin, Nima Fattahi, Rolando Garcia-Milian, Florine Collin, Weiwei Wang, Yohan Kim, Fabrice Lucien, Zhaoli Sun, TuKiet T Lam, John Hwa, Yasuko Iwakiri, Matthew J McConnell","doi":"10.1172/jci.insight.201114","DOIUrl":"10.1172/jci.insight.201114","url":null,"abstract":"Alcohol-associated liver disease (ALD) is a growing global health concern, with alcohol-associated hepatitis (AH) leading to the highest morbidity and mortality. Available therapies are limited and often inadequate. Platelets contribute in a variety of ways to liver disease pathogenesis, but their role in AH remains largely unexplored. In this study, we addressed the hypothesis that platelets contribute to pathological inflammation in AH. Using patient samples and a multiomics approach, we found that platelets undergo proinflammatory transcriptomic and proteomic changes in AH, with 2 alarmins, S100A8 and S100A9, being among the top upregulated genes/proteins. Additionally, the abundance of platelet-derived microparticles containing S100A8 and S100A9 in AH patient plasma was increased and correlated with disease severity (assessed by model for end-stage liver disease sodium [MELD-Na]) and endotheliopathy (assessed by ICAM1, CXCL8, and vWF). We mechanistically linked S100A9 with endotheliopathy via crosstalk between primary human liver sinusoidal endothelial cells and primary human monocytes. We also demonstrated that IL-6 upregulates S100A9 in megakaryocytic cells in a JAK/STAT-dependent manner, modeling changes occurring in the bone marrow in patients with AH. Our studies establish proinflammatory platelets as important contributors to AH pathology. Moreover, antiplatelet agents - or, more specifically, S100A9 targeted drugs - are potential therapeutic strategies in AH.","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"11 16","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808523","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}

引用次数: 0

Navigating physician-scientist careers: insights from American Board of Internal Medicine Research Pathway graduates. 导航医师-科学家的职业生涯：来自美国内科医学研究路径毕业生的见解。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.195683

Emily J Gallagher, Barbara I Kazmierczak, Michael Kisielewski, Nathan Schoettler, Clifford J Steer, Robert A Baiocchi, Jatin M Vyas, Kyu Y Rhee, Patrick J Hu, Carlos M Isales, Paul R Conlin, Christopher D Kontos, Michael Melfe, Furman S McDonald, Don C Rockey, Christopher S Williams

{"title":"Navigating physician-scientist careers: insights from American Board of Internal Medicine Research Pathway graduates.","authors":"Emily J Gallagher, Barbara I Kazmierczak, Michael Kisielewski, Nathan Schoettler, Clifford J Steer, Robert A Baiocchi, Jatin M Vyas, Kyu Y Rhee, Patrick J Hu, Carlos M Isales, Paul R Conlin, Christopher D Kontos, Michael Melfe, Furman S McDonald, Don C Rockey, Christopher S Williams","doi":"10.1172/jci.insight.195683","DOIUrl":"10.1172/jci.insight.195683","url":null,"abstract":"The American Board of Internal Medicine Research Pathway (ABIM RP) is designed to train physician-scientists by shortening postgraduate clinical training and increasing research time. We surveyed ABIM RP graduates to understand career trajectories, research engagement, and barriers to physician-scientist retention in academic research careers. We performed an anonymous, structured, web-based survey of 700 ABIM RP current and former trainees (2011-2022). We received 105 survey responses (97 RP graduates). The survey queried about demographics, training background, career outcomes, research involvement, and perceived barriers to retention in physician-scientist careers. Responses were stratified by trainee status, gender, and Medical Scientist Training Program (MSTP) participation, and select results were compared to test for statistical associations. Most respondents (79%) remained in academia, with 61% engaged in research-dominant roles. More MSTP graduates held research-focused academic positions than non-MSTP graduates. The most commonly reported barriers to sustaining research careers were funding instability, financial concerns, and lack of protected research time. Although many of the trainees in the ABIM RP who completed the survey remained in academia, systemic barriers such as funding instability and gaps in institutional support persist. Strategies to enhance financial stability, protected research time, and mentorship appear to be necessary to enhance physician-scientist career retention.","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"11 16","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808591","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}

引用次数: 0

USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1. USP10通过去泛素化NDUFS1减轻Ang ii诱导的心房重构和房颤易感性。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.195761

Wanrong Fu, Xiao-Xu Tian, Jianghua Zhou, Yu-Xu Huang, Huan Li, Zhenya Wang, Tong-You Wade Wei, Li Li, Guo-Jun Zhao

{"title":"USP10 mitigates Ang II-induced atrial remodeling and atrial fibrillation susceptibility by deubiquitinating NDUFS1.","authors":"Wanrong Fu, Xiao-Xu Tian, Jianghua Zhou, Yu-Xu Huang, Huan Li, Zhenya Wang, Tong-You Wade Wei, Li Li, Guo-Jun Zhao","doi":"10.1172/jci.insight.195761","DOIUrl":"10.1172/jci.insight.195761","url":null,"abstract":"Atrial fibrillation (AF) contributes to cardiovascular morbidity and mortality. Ubiquitin-specific peptidase 10 (USP10) plays a crucial role in numerous cellular processes; however, its particular role in AF remains largely unexplored. In the present study, USP10 expression was assessed in human atrial samples and angiotensin II-treated (Ang II-treated) mouse atrial tissues. An Ang II-induced AF mouse model was employed to investigate the effects of USP10 on atrial remodeling and AF susceptibility. Calcium imaging and patch clamp techniques were used to evaluate USP10's influence on calcium handling and triggered activity. Additionally, RNA sequencing, coimmunoprecipitation, and ubiquitination assays were performed to explore the regulatory interactions between USP10 and NADH:ubiquinone oxidoreductase subunit S1 (NDUFS1). Our findings demonstrate that USP10 is downregulated in atrial tissues from mouse models and patients with AF. USP10 overexpression counteracts Ang II-induced atrial remodeling and reduces AF susceptibility. Furthermore, USP10 contributes to the restoration of mitochondrial function in AF. Mechanistically, USP10 deubiquitinates NDUFS1 at lysine 621, stabilizing NDUFS1 protein levels and mitigating Ang II-induced mitochondrial dysfunction. This study uncovers a critical mechanistic link between USP10 and NDUFS1. Our findings suggest that upregulating USP10 or targeting NDUFS1 degradation could provide an alternative therapeutic strategy to mitigate AF progression and associated cardiovascular risk.","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"11 16","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808614","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}

引用次数: 0

TRANCE is a unique marker of chronic pancreatitis in children. TRANCE是儿童慢性胰腺炎的独特标志。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.198911

Peter R Farrell, Bomi Lee, Faizan Ahmed, Maria E Moreno-Fernandez, Ajay Dixit, Juan Pablo Gurria, Nicholas J Ollberding, Qing Duan, Vineet Garlapally, Phoebe Christian, Sohail Z Husain, Maisam Abu-El-Haija

{"title":"TRANCE is a unique marker of chronic pancreatitis in children.","authors":"Peter R Farrell, Bomi Lee, Faizan Ahmed, Maria E Moreno-Fernandez, Ajay Dixit, Juan Pablo Gurria, Nicholas J Ollberding, Qing Duan, Vineet Garlapally, Phoebe Christian, Sohail Z Husain, Maisam Abu-El-Haija","doi":"10.1172/jci.insight.198911","DOIUrl":"10.1172/jci.insight.198911","url":null,"abstract":"BACKGROUNDElucidating immune signals through well-defined cohorts of pediatric acute pancreatitis (AP) and chronic pancreatitis (CP) patients is critical. This study aimed to evaluate plasma chemokine and cytokine levels in pediatric participants with CP, compared with AP and healthy controls (HCs), to identify unique biomarkers of CP.METHODSIndividuals were identified from a prospectively collected pediatric cohort (n = 146). Immunoproteins (n = 247) were measured using the NULISAseq platform on samples from individuals with CP (n = 71), AP (n = 55), and HCs (n = 20).RESULTSThe measured analytes showed separation among the 3 groups (R2 = 0.13, P < 0.001). In the CP group, TRANCE, TWEAK, FLT-1, HGF, and TRAIL were increased when compared with HC and AP patients (FDR-corrected P <0.05). A multivariable logistic regression model including all 5 proteins provided an AUC of 0.94 (0.93-0.96) for differentiating samples from CP versus AP or HC samples. In the AP group, CRP, IL-6, CD3E, ENRAGE, and MIF were elevated compared with HCs, while FGF-2, TAFA-5, IL-33, TRANCE, and CXCL12 were downregulated in the same acute time period (FDR-corrected P < 0.05). In the 21 patients with AP for whom follow-up samples were obtained, there was a notable decrease in sequential expression of IL-6 and CRP over 12 months and increased expression of CCL25, TAFA-5, and TRANCE proteins. Additionally, TRANCE was expressed on CP pancreatic tissue.CONCLUSIONSTRANCE was increased in pediatric patients with CP and decreased in those with AP during a flare. Future studies are needed to investigate the role of TRANCE and other analytes in the pathogenesis of CP.","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"11 16","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808521","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}

引用次数: 0

Reduced dosage of Kmt2d modifies Tbx1 haploinsufficiency toward phenotypes of 22q11.2DS. 减少Kmt2d剂量可改变Tbx1单倍体缺陷对22q11.2DS表型的影响。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-24 DOI: 10.1172/jci.insight.206763

Daniella Miller, Kevyn Jackson, Timothy C Cox, Bernice E Morrow

{"title":"Reduced dosage of Kmt2d modifies Tbx1 haploinsufficiency toward phenotypes of 22q11.2DS.","authors":"Daniella Miller, Kevyn Jackson, Timothy C Cox, Bernice E Morrow","doi":"10.1172/jci.insight.206763","DOIUrl":"10.1172/jci.insight.206763","url":null,"abstract":"Haploinsufficiency of TBX1, which occurs in 22q11.2 deletion syndrome (22q11.2DS), leads to a heterogeneous spectrum of clinical manifestations, including craniofacial anomalies, immunodeficiency, and congenital heart defects. The variability in syndromic presentation between patients may be partially explained by variants in chromatin regulatory genes that act to further modify TBX1 function. To investigate this relationship, we selected KMT2D as a candidate gene because of its role in the etiology of Kabuki syndrome, which shares overlapping features with 22q11.2DS. We demonstrate that conditional inactivation of Kmt2d in the Tbx1 lineage in Tbx1-heterozygous mice leads to fully penetrant perinatal lethality and increased incidence of craniofacial dysmorphism, thymus and parathyroid gland hypoplasia, and aortic arch anomalies. At early stages, mutant embryos were found to have defects of the caudal pharyngeal apparatus, including abnormal patterning of the third pouch endoderm, hypoplastic fourth arches, and defective fourth arch arteries. Finally, analysis of single-cell RNA sequencing revealed dysregulation, and largely downregulation, of genes involved in basic cellular functions, suggesting that Tbx1 and Kmt2d developmentally converge upon essential biological processes. Overall, these results indicate that reduced dosage of Kmt2d perturbs the developmental landscape of the Tbx1 heterozygote, eliciting phenotypes that are shared between 22q11.2DS and Kabuki syndrome.","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"11 16","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13502172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808555","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}

引用次数: 0

Time-restricted feeding reverses kidney fibrosis through reducing CD8+ T cell infiltration in obese mice. 限时喂养通过减少肥胖小鼠的CD8+ T细胞浸润逆转肾纤维化。

IF 6.8 1区医学

JCI insight Pub Date : 2026-08-20 eCollection Date: 2026-10-08 DOI: 10.1172/jci.insight.195335

Claudia J Edell, John D Erickson, Xiaofen Liu, Savannah C Walker, Jackson Colson, Michael Heim, Pranav Nagila, Kyle H Moore, Keri M Kemp, Kelly Hyndman, Selene Meza-Perez, Troy D Randall, Annye P Bennett, Anna G Sorace, Yu-Hua Dean Fang, David M Pollock, Carmen De Miguel, Julienne L Carstens, Jennifer S Pollock

{"title":"Time-restricted feeding reverses kidney fibrosis through reducing CD8+ T cell infiltration in obese mice.","authors":"Claudia J Edell, John D Erickson, Xiaofen Liu, Savannah C Walker, Jackson Colson, Michael Heim, Pranav Nagila, Kyle H Moore, Keri M Kemp, Kelly Hyndman, Selene Meza-Perez, Troy D Randall, Annye P Bennett, Anna G Sorace, Yu-Hua Dean Fang, David M Pollock, Carmen De Miguel, Julienne L Carstens, Jennifer S Pollock","doi":"10.1172/jci.insight.195335","DOIUrl":"10.1172/jci.insight.195335","url":null,"abstract":"Obesity is a major risk factor for chronic kidney disease. Time-restricted feeding (TRF) shows promise to reduce kidney inflammation in chronic kidney disease. We hypothesized that TRF blunts kidney fibrosis in obese mice by mitigating T cell inflammation. We used a diet-induced obese mouse model fed a high-fat diet (DIO; 45% fat) ad libitum for 18 weeks followed by 2 weeks of TRF or ad libitum high-fat feeding. We found that TRF reversed kidney fibrosis as well as reduced kidney CD8+ T cells in DIO mice. Our study also reveals that DIO mice had increased kidney CD8+ T cell infiltration from the small intestine that was blunted with TRF. Furthermore, anti-CD8 intervention in DIO showed reduced kidney fibrosis and damage compared with anti-IgG-treated DIO mice. Single-cell RNA-seq data reveal that DIO increased, while TRF reduced, the frequency of a specific cluster of CD8+ T cells that featured high expression of exhaustion/activation genes. Spatial analyses showed DIO mice had significant infiltration of PD-1+CD8+ T cells near CD31+ endothelial cells that was diminished by TRF. In conclusion, this study shows that TRF reversed kidney fibrosis through reducing CD8+ T cell infiltration in obese mice.","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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