Mihai Avram, Aurore Menegaux, Felix Müller, Hannes Zaczek, Alexandra Korda, Helena Rogg, Anna M Becker, Laura Ley, Matthias E Liechti, Stefan Borgwardt
{"title":"Neuroplastic white matter changes in patients with major depression following lysergic acid diethylamide treatment.","authors":"Mihai Avram, Aurore Menegaux, Felix Müller, Hannes Zaczek, Alexandra Korda, Helena Rogg, Anna M Becker, Laura Ley, Matthias E Liechti, Stefan Borgwardt","doi":"10.1016/j.xcrm.2026.102791","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102791","url":null,"abstract":"<p><p>The clinical trial NCT03866252 investigates the antidepressant effects of lysergic acid diethylamide (LSD) in 61 patients with major depressive disorder (MDD) randomized to low-dose LSD (LD-LSD; 2 × 25 μg) or moderate-to-high-dose LSD (HD-LSD; 100 μg followed by 200 μg) 4 weeks apart. Although the trial reports positive clinical outcomes, underlying mechanisms remain unclear. Here, we test whether LSD alters white matter (WM) microstructure, potentially reflecting enhanced neuroplasticity. Diffusion tensor imaging data from 35 patients (17 HD-LSD) include pre- and post-intervention scans. Voxel-wise permutation tests reveal group-by-time interactions, with increased fractional anisotropy (FA) in the internal and external capsule, sagittal stratum, and fornix/stria terminalis in the HD-LSD group. In this group, post-intervention FA values correlate with improvements in depressive symptoms at 2, 6, and 12 weeks, measured using the Inventory of Depressive Symptomatology (IDS-clinician rated [C] and IDS- self report [SR]). These findings suggest that LSD-induced WM microstructural changes are associated with antidepressant effects in MDD.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102791"},"PeriodicalIF":10.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855932","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}
Kiva Brennan, Ema Ozaki, Eleanor Noone, Sarah Palko, Kieran P Byrne, Fiona Roche, Matt McElheron, Kieva Byrne, Luke Gibbons, Katie Robb, Said Aktas, Emma Connolly, Natalie Hudson, Matthew M O'Riordan, Dara O'Boyle, Rachel Dalton, Aline Zoller, Erin Fahey, Karsten Hokamp, Derrick Feenstra, Nollaig Bourke, Matthew Campbell, David Finlay, Kelly Mulfaul, Robert F Mullins, Rose Anne Kenny, Mark T Cahill, Sarah L Doyle
{"title":"Circulating natural killer cells are phenotypically and functionally altered in age-related macular degeneration.","authors":"Kiva Brennan, Ema Ozaki, Eleanor Noone, Sarah Palko, Kieran P Byrne, Fiona Roche, Matt McElheron, Kieva Byrne, Luke Gibbons, Katie Robb, Said Aktas, Emma Connolly, Natalie Hudson, Matthew M O'Riordan, Dara O'Boyle, Rachel Dalton, Aline Zoller, Erin Fahey, Karsten Hokamp, Derrick Feenstra, Nollaig Bourke, Matthew Campbell, David Finlay, Kelly Mulfaul, Robert F Mullins, Rose Anne Kenny, Mark T Cahill, Sarah L Doyle","doi":"10.1016/j.xcrm.2026.102792","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102792","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) is the leading cause of irreversible central blindness and can result in pathological neovascularization. Using a \"human-first\" approach, we identify immunotherapy as a disease modifier in models of neovascular AMD (nAMD). Plasma cytokine analysis in a large population cohort reveals an imbalance of lymphocytic cytokines associated with severity of AMD, leading to discovery of a skewed peripheral natural killer (NK) cell phenotype in individuals with AMD. Peripheral NK cells are rapidly activated in nAMD models, and single-cell RNA sequencing demonstrates expansion of activated cytolytic NK cells within neovascular lesions during resolution. NK cells localize to neovessels in human AMD donor eyes; however, they exhibit markers of terminal differentiation and quiescence. Adoptive transfer of pre-activated NK cells reduces neovascularization and restores barrier integrity. Our data identify a distinct, functionally altered NK cell phenotype in nAMD and suggests harnessing NK cells represents an immunotherapeutic alternative for the treatment of nAMD.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102792"},"PeriodicalIF":10.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855979","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}
Veselina Petrova, Caitlin E Mills, Clemens Hug, Aysel Cetinkaya-Fisgin, Jennifer Splaine, Sepideh Fouladzadeh, Sara Hakim, Rasheen Powell, Shannon Zhen, Mirra Chung, Gary A Bradshaw, Tao Deng, Ilyas Singec, Qing Wang, Riki Kawaguchi, Harathi Jonnagaddala, Lee B Barrett, Jennifer A Smith, Marian Kalocsay, Benjamin M Gyori, Ahmet Hoke, Peter K Sorger, Clifford J Woolf
{"title":"A human iPSC-derived sensory neuron platform for high-throughput discovery of neuroprotectants against chemotherapy-induced peripheral neuropathy.","authors":"Veselina Petrova, Caitlin E Mills, Clemens Hug, Aysel Cetinkaya-Fisgin, Jennifer Splaine, Sepideh Fouladzadeh, Sara Hakim, Rasheen Powell, Shannon Zhen, Mirra Chung, Gary A Bradshaw, Tao Deng, Ilyas Singec, Qing Wang, Riki Kawaguchi, Harathi Jonnagaddala, Lee B Barrett, Jennifer A Smith, Marian Kalocsay, Benjamin M Gyori, Ahmet Hoke, Peter K Sorger, Clifford J Woolf","doi":"10.1016/j.xcrm.2026.102787","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102787","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of cancer treatment, yet the lack of predictive human models continues to hinder therapeutic progress. Here, we establish a scalable and reproducible model of paclitaxel-induced axon degeneration and neurotoxicity in human iPSC-derived sensory neurons, suitable for high-throughput identification of neuroprotective compounds. Using this platform, we screen a library of 192 kinase inhibitors and identify 19 hits that commonly inhibit three STE20 kinases-MAP4K4, MINK1, and TNIK. Genetic knockdown studies reveal that multi-kinase inhibition of these kinases is required for neuroprotection against paclitaxel. Consistently, selective pharmacological inhibition of the identified STE20 kinases rescues paclitaxel-induced axon degeneration in iPSC-derived sensory neurons and primary human dorsal root ganglia (DRG) and preserves intraepidermal nerve fiber density in a mouse model of CIPN. Together, these findings establish a translational human sensory neuron platform that enables target validation and drug discovery for CIPN.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102787"},"PeriodicalIF":10.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834096","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}
Alexis Onimus, Daiana Celias, Shiun Chang, Joshua Davis, Jay Mandula, Jie Li, Alycia Gardner, Kay Hänggi, Olabisi Osunmakinde, Hatem Soliman, Timothy I Shaw, Paulo C Rodriguez, Brian Ruffell
{"title":"Taxane chemotherapy promotes response to TIM-3 checkpoint blockade via STING-mediated ER stress and HMGB1 secretion.","authors":"Alexis Onimus, Daiana Celias, Shiun Chang, Joshua Davis, Jay Mandula, Jie Li, Alycia Gardner, Kay Hänggi, Olabisi Osunmakinde, Hatem Soliman, Timothy I Shaw, Paulo C Rodriguez, Brian Ruffell","doi":"10.1016/j.xcrm.2026.102788","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102788","url":null,"abstract":"<p><p>Immune checkpoint inhibitors are increasingly being used in conjunction with chemotherapy regimens, but the reasons for the success or failure of these combinations remains unclear. In previous studies, we described how blocking TIM-3 promotes activation of dendritic cells through HMGB1-dependent DNA uptake, resulting in efficacy when combined with paclitaxel. Here, we show that the release of HMGB1 by tumor cells is required for the combinatorial efficacy with TIM-3 blockade observed with paclitaxel, docetaxel, fluorouracil, and irradiation. HMGB1 release during taxane therapy is an active process involving nuclear export following Toll-like receptor 4 (TLR4)-dependent reactive oxygen species production, DNA damage, and poly(ADP-ribose) polymerase activation. DNA damage promotes the accumulation of cytosolic double-stranded DNA (dsDNA), which activates the cGAS-STING pathway; however, taxanes fail to induce type I interferons. Instead, STING activation promotes endoplasmic reticulum (ER) stress and lysosomal exocytosis, driving HMGB1 secretion. Thus, non-canonical STING signaling in response to taxanes can promote the efficacy of chemoimmunotherapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102788"},"PeriodicalIF":10.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834216","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}
David A Braun, Marcus S Noel, Ryan H Moy, Kurt Demel, Martin Gutierrez, Sunil Sharma, Arif Hussain, Shirish Gadgeel, Julio Peguero, Toni K Choueiri, Hamid Emamekhoo, Brian Van Tine, Rama Balaraman, GiNell Elliott, Sritama Nath, Scott R Daigle, Pavan Kumar, Anita Scheuber, David Sommerhalder
{"title":"HPK1 inhibitor NDI-101150 as monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: Phase 1/2 trial results.","authors":"David A Braun, Marcus S Noel, Ryan H Moy, Kurt Demel, Martin Gutierrez, Sunil Sharma, Arif Hussain, Shirish Gadgeel, Julio Peguero, Toni K Choueiri, Hamid Emamekhoo, Brian Van Tine, Rama Balaraman, GiNell Elliott, Sritama Nath, Scott R Daigle, Pavan Kumar, Anita Scheuber, David Sommerhalder","doi":"10.1016/j.xcrm.2026.102789","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102789","url":null,"abstract":"<p><p>Hematopoietic progenitor kinase 1 (HPK1) induces potent anti-tumor immunity in preclinical models by activating and recruiting T cells, B cells, and dendritic cells into the tumor microenvironment (TME). Here, we evaluate NDI-101150, a potent, selective HPK1 inhibitor, in a phase 1/2 trial as a monotherapy or in combination with pembrolizumab in patients with advanced solid tumors. The monotherapy maximum tolerated dose (MTD) is 150 mg once daily, and doses tested up to 100 mg once daily are combinable with pembrolizumab without reaching an MTD. In clear cell renal cell carcinoma, the investigator-assessed overall response rate with monotherapy treatment is 13.6%, including one complete response and two partial responses, with a clinical benefit rate of 27.3% and a disease control rate of 54.5%. Pharmacodynamic analyses show pharmacodynamic biomarker phospho-SLP76 inhibition and increased activated CD8<sup>+</sup> T cells and dendritic cells in the TME, supporting continued development (clinical registration number NCT05128487).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102789"},"PeriodicalIF":10.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834091","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}
Julian Chua, Arshdeep Kaur, Fynnis Mitchell, Anneke Korver, Parnika Sakthivel, Elleine Allapitan, Mahdin Uddin, Areeba Maqsood, Naomi Chege, Aralia Leon-Coria, Constance A M Finney, Oliver F Bathe, Parham Minoo, Arshad Ayyaz
{"title":"A tumor-intrinsic WNT-inhibitory NOTUM program drives immune resistance in microsatellite stable colorectal cancer.","authors":"Julian Chua, Arshdeep Kaur, Fynnis Mitchell, Anneke Korver, Parnika Sakthivel, Elleine Allapitan, Mahdin Uddin, Areeba Maqsood, Naomi Chege, Aralia Leon-Coria, Constance A M Finney, Oliver F Bathe, Parham Minoo, Arshad Ayyaz","doi":"10.1016/j.xcrm.2026.102776","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102776","url":null,"abstract":"<p><p>Immunotherapy remains largely ineffective in colorectal cancer (CRC), particularly in microsatellite stable (MSS) tumors, which represent the majority of cases. However, the complexity of intratumoral heterogeneity has made it difficult to define tumor-intrinsic programs that drive immune resistance. Here, we identify a cancer cell population that emerges predominantly in advanced-stage MSS CRCs. These cells exhibit stem-like features but aberrantly activate a WNT-inhibitory transcriptional program marked by high NOTUM expression. We term these cells WNT/β-catenin inhibitory cancer cells (WICCs). WICCs are enriched in immune-excluded tumors, correlate with reduced CD8<sup>+</sup> T cell infiltration, and are induced in both primary human CRC tumors and patient-derived tumoroids. Selective ablation of WICCs or genetic knockout of NOTUM enhances CD8<sup>+</sup> T-cell-mediated cytotoxicity, uncovering a tumor-intrinsic mechanism of immune evasion and nominating the WICC-NOTUM axis as a selective and tractable therapeutic target to overcome immunotherapy resistance in CRC.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102776"},"PeriodicalIF":10.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834055","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}
Guillaume Mestrallet, Matthew Brown, Natalie Vaninov, Nam Woo Cho, Leandra Velazquez, Aparna Ananthanarayanan, Matthew Spitzer, Nicolas Vabret, Cansu Cimen Bozkus, Robert M Samstein, Nina Bhardwaj
{"title":"Reprogramming T cell-myeloid crosstalk overcomes immune resistance in colorectal cancer.","authors":"Guillaume Mestrallet, Matthew Brown, Natalie Vaninov, Nam Woo Cho, Leandra Velazquez, Aparna Ananthanarayanan, Matthew Spitzer, Nicolas Vabret, Cansu Cimen Bozkus, Robert M Samstein, Nina Bhardwaj","doi":"10.1016/j.xcrm.2026.102786","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102786","url":null,"abstract":"<p><p>Colorectal cancer (CRC) accounts for 10% of cancer cases and is the second leading cause of cancer-related deaths. Although anti-PD-1 therapy improves outcomes, 50% of advanced mismatch repair-deficient (MMRd) and most mismatch repair-proficient (MMRp) CRC cases fail to respond. Using orthotopic and patient-derived CRC models with single-cell and spatial analyses, we show that tumor control during anti-PD-1 treatment associates with colocalization of MHC<sup>+</sup> C1Q<sup>+</sup> CXCL9<sup>+</sup> macrophages and TCF<sup>+</sup> PRF1<sup>+</sup> T cells. Resistance correlates with increased TIM3, LAG3, TIGIT, and PD-1 expression on T cells and enrichment of TREM2<sup>+</sup> macrophages in T cell-excluded regions. A combinatorial blockade targeting TREM2, LAG3, CTLA4, and PD-1 induces up to 100% tumor clearance in MMRd and >70% in MMRp models. This strategy promotes immune memory mediated by interactions among MHC<sup>+</sup> macrophages and CD4<sup>+</sup>/CD8<sup>+</sup>/TCF<sup>+</sup> T cells, while reducing immunosuppressive myeloid infiltration and T cell exhaustion, identifying key cellular programs that overcome immune escape in CRC.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102786"},"PeriodicalIF":10.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834194","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}
Alexios N Matralis, Elli-Anna Stylianaki, Eleni M Ladopoulou, Paraskevi Kanellopoulou, Stefanos Smyrniotis, Christiana Magkrioti, Konstantinos D Papavasileiou, Sabine Willems, Juan Pablo Rincon Pabon, Dimitris Nastos, Alexandros Galaras, Céline Moro, Skarlatos G Dedos, Eleanna Kaffe, Pantelis Hatzis, Hanan Osman-Ponchet, Daniel Merk, Argyris Politis, Antreas Afantitis, Ioulia Tseti, Katerina M Antoniou, Athol U Wells, Vassilis Aidinis
{"title":"An aerosolized dual-action autotaxin inhibitor-PPARγ agonist for the treatment of pulmonary fibrosis.","authors":"Alexios N Matralis, Elli-Anna Stylianaki, Eleni M Ladopoulou, Paraskevi Kanellopoulou, Stefanos Smyrniotis, Christiana Magkrioti, Konstantinos D Papavasileiou, Sabine Willems, Juan Pablo Rincon Pabon, Dimitris Nastos, Alexandros Galaras, Céline Moro, Skarlatos G Dedos, Eleanna Kaffe, Pantelis Hatzis, Hanan Osman-Ponchet, Daniel Merk, Argyris Politis, Antreas Afantitis, Ioulia Tseti, Katerina M Antoniou, Athol U Wells, Vassilis Aidinis","doi":"10.1016/j.xcrm.2026.102778","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102778","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic interstitial lung disease (ILD) with limited therapeutic options. Autotaxin (ATX), an established drug target in IPF, is a secreted lysophospholipase D that catalyzes the extracellular production of lysophosphatidic acid (LPA), a growth-factor-like signaling phospholipid. The many pathologic effects of LPA in the lung include the co-suppression of peroxisome-proliferator-activated receptor γ (PPARγ), a therapeutic target in metabolic disorders. In this report, we introduce EL244, a dual ATX inhibitor and PPARγ agonist endowed with drug-like properties. Developed through repositioning, rational design, targeted synthesis, and pharmacological characterization, EL244 exhibited favorable efficacy and physicochemical profiles. Inhalation of EL244, which alleviates systemic toxicity concerns, attenuated bleomycin (BLM)-induced pulmonary fibrosis and restored respiratory functions; in translation, EL244 attenuated fibrosis in human fibrotic precision-cut lung slices (PCLSs). Therefore, EL244 emerges as a promising clinical candidate for the inhaled treatment of IPF and ILDs.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102778"},"PeriodicalIF":10.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811640","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}
{"title":"Cross-tissue atlas of mucosa-associated lymphoid tissue lymphomas reveals intratumoral heterogeneity and microenvironmental subtypes.","authors":"Kai Kang, Yijun Wu, Xu Sun, Yuqi Yang, Wenyi Liang, Jinrong Yang, Yun Tang, Bing Xiang, Ting Niu, Ailin Zhao","doi":"10.1016/j.xcrm.2026.102785","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102785","url":null,"abstract":"<p><p>Mucosa-associated lymphoid tissue (MALT) lymphoma, a common primary extranodal B cell lymphoma that arises in diverse mucosal tissues, has a pathogenesis closely linked to the supportive lymphoma microenvironment (LME). However, its microenvironmental heterogeneity and therapeutic implications remain unclear. Here, we report a cohort of 89 MALT lymphoma samples from multiple anatomical sites, profiled by bulk (n = 89), single-nucleus (n = 16), and spatial (n = 9) RNA sequencing. Integrative analysis of 120 bulk transcriptomes from our cohort and two independent cohorts, guided by cell-type-resolved signatures derived from single-nucleus data, identifies three LME subtypes: mesenchymal, inflammatory, and depleted. Single-cell and spatial mapping further reveal distinct cellular compositions and interaction networks across these subtypes, particularly in relation to B cell activation and angiogenesis, suggesting distinct biological states and subtype-specific therapeutic vulnerabilities. This study establishes an LME-based classification framework for MALT lymphoma with biological and clinical relevance.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102785"},"PeriodicalIF":10.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811623","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}
Junhua Xie, Xi-Jian Dai, Qiqiong Li, Wanyu Zhang, Xinke Nie, Haihua Ji, Xinyang Chen, Yuchen Wang, Jing Feng, Zhipeng Li, Qiong Liu, Jianxin Ye, Guangzhi Zhang, Shaoping Nie
{"title":"Escherichia coli Nissle 1917 alleviates Alzheimer's disease in mice through OmpA-containing outer membrane vesicles.","authors":"Junhua Xie, Xi-Jian Dai, Qiqiong Li, Wanyu Zhang, Xinke Nie, Haihua Ji, Xinyang Chen, Yuchen Wang, Jing Feng, Zhipeng Li, Qiong Liu, Jianxin Ye, Guangzhi Zhang, Shaoping Nie","doi":"10.1016/j.xcrm.2026.102781","DOIUrl":"https://doi.org/10.1016/j.xcrm.2026.102781","url":null,"abstract":"<p><p>Gut microbiota dysbiosis is a driving factor in Alzheimer's disease (AD), yet the mechanisms behind remain elusive. Emerging evidence highlights that outer membrane vesicles (OMVs) are critical mediators of microbiota-host communication. Here, we observed a reduction in a gut probiotic Escherichia coli Nissle 1917 (EcN)-like strain in AD patients, and its levels are positively associated with cognitive ability. The EcN OMVs containing outer membrane protein A (OmpA) translocate to the brain, reshaping the dysregulated immune network. Specifically, EcN OMVs are internalized by glia and neurons, suppressing glial hyperactivation and restoring synaptic function, thereby reducing Aβ deposition and cognitive deficits. The results further show that OmpA plays an important role in vesicle trafficking and inflammatory pathways and may be the key regulator of inflammatory mediators in EcN OMVs, modulating astrocyte-microglia-neuron interactions and functionality. This work discloses the substantial therapeutic potential of the probiotic and its secreted OMVs in intervention and treatment of neurological disorders.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102781"},"PeriodicalIF":10.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811700","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
