Journal of Experimental Medicine最新文献_第4页

Aging microvasculature: Effects on immune cell trafficking and inflammatory diseases. 衰老微血管：对免疫细胞运输和炎症性疾病的影响。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-07-07 Epub Date: 2025-06-02 DOI: 10.1084/jem.20242154

Natalia Reglero-Real, Loïc Rolas, Sussan Nourshargh

引用次数: 0

Tumor cell heterogeneity drives spatial organization of the intratumoral immune response. 肿瘤细胞异质性驱动肿瘤内免疫反应的空间组织。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-04-01 DOI: 10.1084/jem.20242282

Miho Tanaka, Lotus Lum, Kenneth H Hu, Piyush Chaudhary, Savannah Hughes, Cecilia Ledezma-Soto, Bushra Samad, Daphne Superville, Kenneth Ng, Arun Chumber, Ciara Benson, Zoe N Adams, Kelly Kersten, Oscar A Aguilar, Lawrence Fong, Alexis J Combes, Matthew F Krummel, Melissa Q Reeves

{"title":"Tumor cell heterogeneity drives spatial organization of the intratumoral immune response.","authors":"Miho Tanaka, Lotus Lum, Kenneth H Hu, Piyush Chaudhary, Savannah Hughes, Cecilia Ledezma-Soto, Bushra Samad, Daphne Superville, Kenneth Ng, Arun Chumber, Ciara Benson, Zoe N Adams, Kelly Kersten, Oscar A Aguilar, Lawrence Fong, Alexis J Combes, Matthew F Krummel, Melissa Q Reeves","doi":"10.1084/jem.20242282","DOIUrl":"10.1084/jem.20242282","url":null,"abstract":"Intratumoral heterogeneity (ITH)-defined as genetic and cellular diversity within a tumor-is linked to failure of immunotherapy and an inferior anti-tumor immune response. We modeled heterogeneous tumors comprised of \"hot\" and \"cold\" tumor populations (giving rise to T cell-rich and T cell-poor tumors, respectively) and introduced fluorescent labels to enable precise spatial tracking. We found the cold tumor cell population exerted a \"dominant cold\" effect in mixed tumors. Strikingly, spatial analysis revealed that the tumor cells themselves created distinct local microenvironments within heterogeneous tumors: regions occupied by cold tumor cells showed pronounced immunosuppression, harboring increased CD206Hi macrophages and diminished local T cell function. This inferior T cell activity in cold regions persisted even after immunotherapy and mechanistically was mediated by CX3CL1 produced by the cold tumor cells. An immune cold tumor population within a heterogeneous tumor thus impairs tumor immunity on both a tumor-wide and a highly localized spatial scale.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 6","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752890","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

Correction: Transcription of HIV-1 at sites of intact latent provirus integration. 更正：HIV-1在完整潜伏前病毒整合位点的转录。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-05-23 DOI: 10.1084/jem.2024039105162025c

Ana Rafaela Teixeira, Cintia Bittar, Gabriela S Silva Santos, Thiago Y Oliveira, Amy S Huang, Noemi Linden, Isabella A T M Ferreira, Tetyana Murdza, Frauke Muecksch, R Brad Jones, Marina Caskey, Mila Jankovic, Michel C Nussenzweig

引用次数: 0

Breast cancer gene-1 (BRCA1) potentiates maladaptive repair after kidney injury. 乳腺癌基因1 （BRCA1）增强肾损伤后的不适应修复。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-03-28 DOI: 10.1084/jem.20231107

Amrendra K Ajay, Akinwande A Akinfolarin, Cody C Gifford, Venkata S Sabbisetti, Joseph V Bonventre

{"title":"Breast cancer gene-1 (BRCA1) potentiates maladaptive repair after kidney injury.","authors":"Amrendra K Ajay, Akinwande A Akinfolarin, Cody C Gifford, Venkata S Sabbisetti, Joseph V Bonventre","doi":"10.1084/jem.20231107","DOIUrl":"10.1084/jem.20231107","url":null,"abstract":"Maladaptive repair following kidney tubular injury leads to the development of interstitial fibrosis, a pathology common to chronic kidney diseases (CKD). Dysfunctional DNA damage response plays an important role in the progression of CKD. We found that BRCA1 expression was increased in the kidneys of patients with CKD and fibrotic kidneys of mice. Exon 11 deletion of Brca1 in proximal tubule cells (PTCs) of mice subjected to ischemic or nephrotoxic (aristolochic acid) injury resulted in a reduced number of senescent cells, as assessed by a decrease in phospho-histone H3, p16INK4a, RAD51 recruitment, G2/M cell cycle phase cells, GATA4, and senescence-associated β-galactosidase. There was less production of inflammatory profibrotic mediators and reduced kidney fibrosis. After cisplatin exposure in vitro, human PTCs with reduced BRCA1 had increased apoptosis, decreased RAD51 nuclear foci, and fewer cells in the G2/M cell cycle phase, with reduced IL-6 and sonic hedgehog production. Thus, BRCA1 regulates nonmalignant tissue responses to kidney injury, a role hitherto unrecognized.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 6","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728755","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

Age- and diet-instructed metabolic rewiring of the tumor-immune microenvironment. 年龄和饮食指示的肿瘤免疫微环境的代谢重新布线。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-04-11 DOI: 10.1084/jem.20241102

Ana Belén Plata-Gómez, Ping-Chih Ho

{"title":"Age- and diet-instructed metabolic rewiring of the tumor-immune microenvironment.","authors":"Ana Belén Plata-Gómez, Ping-Chih Ho","doi":"10.1084/jem.20241102","DOIUrl":"https://doi.org/10.1084/jem.20241102","url":null,"abstract":"The tumor-immune microenvironment (TIME) plays a critical role in tumor development and metastasis, as it influences the evolution of tumor cells and fosters an immunosuppressive state by intervening the metabolic reprogramming of infiltrating immune cells. Aging and diet significantly impact the metabolic reprogramming of the TIME, contributing to cancer progression and immune evasion. With aging, immune cell function declines, leading to a proinflammatory state and metabolic alterations such as increased oxidative stress and mitochondrial dysfunction, which compromise antitumor immunity. Similarly, dietary factors, particularly high-fat and high-sugar diets, promote metabolic shifts, creating a permissive TIME by fostering tumor-supportive immune cell phenotypes while impairing the tumoricidal activity of immune cells. In contrast, dietary restrictions have been shown to restore immune function by modulating metabolism and enhancing antitumor immune responses. Here, we discuss the intricate interplay between aging, diet, and metabolic reprogramming in shaping the TIME, with a particular focus on T cells, and highlight therapeutic strategies targeting these pathways to empower antitumor immunity.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 6","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021144","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

Hiding in plain sight: A new lymphoid organ discovered in zebrafish. 隐藏在显眼的地方：在斑马鱼身上发现了一个新的淋巴器官。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-04-18 DOI: 10.1084/jem.20250321

Mohamed N Bakr, David M Langenau

引用次数: 0

Laura Mackay: Don't be afraid to engage. 劳拉·麦凯：不要害怕参与。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-05-13 DOI: 10.1084/jem.20250876

Lucie Van Emmenis

引用次数: 0

Correction: Chromatin landscapes reveal developmentally encoded transcriptional states that define human glioblastoma. 更正：染色质景观揭示了定义人类胶质母细胞瘤的发育编码转录状态。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-05-20 DOI: 10.1084/jem.2019019605052025C

Stephen C Mack, Irtisha Singh, Xiuxing Wang, Rachel Hirsch, Quilian Wu, Rosie Villagomez, Jean A Bernatchez, Zhe Zhu, Ryan C Gimple, Leo J Y Kim, Andrew Morton, Sisi Lai, Zhixin Qiu, Briana C Prager, Kelsey C Bertrand, Clarence Mah, Wenchao Zhou, Christine Lee, Gene H Barnett, Michael A Vogelbaum, Andrew E Sloan, Lukas Chavez, Shideng Bao, Peter C Scacheri, Jair L Siqueira-Neto, Charles Y Lin, Jeremy N Rich

引用次数: 0

Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design. I型干扰素自身抗体足迹揭示中和机制，并允许抑制诱饵设计。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-03-20 DOI: 10.1084/jem.20242039

Kevin Groen, Roger Kuratli, Jannik Enkelmann, Sonja Fernbach, Pedro D Wendel-Garcia, Willy I Staiger, Marylène Lejeune, Esther Sauras-Colón, Ferran Roche-Campo, Paraskevas Filippidis, Andri Rauch, Alexandra Trkola, Huldrych F Günthard, Roger D Kouyos, Silvio D Brugger, Benjamin G Hale

{"title":"Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design.","authors":"Kevin Groen, Roger Kuratli, Jannik Enkelmann, Sonja Fernbach, Pedro D Wendel-Garcia, Willy I Staiger, Marylène Lejeune, Esther Sauras-Colón, Ferran Roche-Campo, Paraskevas Filippidis, Andri Rauch, Alexandra Trkola, Huldrych F Günthard, Roger D Kouyos, Silvio D Brugger, Benjamin G Hale","doi":"10.1084/jem.20242039","DOIUrl":"10.1084/jem.20242039","url":null,"abstract":"Autoantibodies neutralizing type I interferons (IFN-Is; IFNα or IFNω) exacerbate severe viral disease, but specific treatments are unavailable. With footprint profiling, we delineate two dominant IFN-I faces commonly recognized by neutralizing IFN-I autoantibody-containing plasmas from aged individuals with HIV-1 and from individuals with severe COVID-19. These faces overlap with IFN-I regions independently essential for engaging the IFNAR1/IFNAR2 heterodimer, and neutralizing plasmas efficiently block the interaction of IFN-I with both receptor subunits in vitro. In contrast, non-neutralizing autoantibody-containing plasmas limit the interaction of IFN-I with only one receptor subunit and display relatively low IFN-I-binding avidities, thus likely hindering neutralizing function. Iterative engineering of signaling-inert mutant IFN-Is (simIFN-Is) retaining dominant autoantibody targets created potent decoys that prevent IFN-I neutralization by autoantibody-containing plasmas and that restore IFN-I-mediated antiviral activity. Additionally, microparticle-coupled simIFN-Is were effective at depleting IFN-I autoantibodies from plasmas, leaving antiviral antibodies unaffected. Our study reveals mechanisms of action for IFN-I autoantibodies and demonstrates a proof-of-concept strategy to alleviate pathogenic effects.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 6","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663552","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

Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells. 显性干扰CARD11变体破坏JNK信号以促进T细胞中GATA3的表达。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2025-06-02 Epub Date: 2025-03-20 DOI: 10.1084/jem.20240272

Bradly M Bauman, Jeffrey R Stinson, Melissa A Kallarakal, Lei Haley Huang, Andrew M Frank, Gauthaman Sukumar, Nermina Saucier, Clifton L Dalgard, Alice Y Chan, Joshua D Milner, Megan A Cooper, Andrew L Snow

{"title":"Dominant interfering CARD11 variants disrupt JNK signaling to promote GATA3 expression in T cells.","authors":"Bradly M Bauman, Jeffrey R Stinson, Melissa A Kallarakal, Lei Haley Huang, Andrew M Frank, Gauthaman Sukumar, Nermina Saucier, Clifton L Dalgard, Alice Y Chan, Joshua D Milner, Megan A Cooper, Andrew L Snow","doi":"10.1084/jem.20240272","DOIUrl":"10.1084/jem.20240272","url":null,"abstract":"Several \"primary atopic disorders\" are linked to monogenic defects that attenuate TCR signaling, favoring T helper type 2 (TH2) cell differentiation. Patients with CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease suffer from severe atopy, caused by germline loss-of-function/dominant interfering (LOF/DI) CARD11 variants. The CARD11 scaffold enables TCR-induced activation of NF-κB, mTORC1, and JNK signaling, yet the function of CARD11-dependent JNK signaling in T cells remains nebulous. Here we show that CARD11 is critical for TCR-induced activation of JNK1 and JNK2, as well as canonical JUN/FOS AP-1 family members. Patient-derived CARD11 DI variants attenuated WT CARD11 JNK signaling, mirroring effects on NF-κB. Transcriptome profiling revealed JNK inhibition upregulated TCR-induced expression of GATA3 and NFATC1, key transcription factors for TH2 cell development. Further, impaired CARD11-JNK signaling was linked to enhanced GATA3 expression in CADINS patient T cells. Our findings reveal a novel intrinsic mechanism connecting impaired CARD11-dependent JNK signaling to enhanced GATA3/NFAT2 induction and TH2 cell differentiation in CADINS patients.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 6","pages":""},"PeriodicalIF":12.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663551","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