Journal of Experimental Medicine最新文献_第5页

Transcriptional network dynamics in early T cell development. 早期 T 细胞发育过程中的转录网络动力学

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-08-21 DOI: 10.1084/jem.20230893

Boyoung Shin, Samantha J Chang, Brendan W MacNabb, Ellen V Rothenberg

引用次数: 0

A path forward for Staphylococcus aureus vaccine development. 金黄色葡萄球菌疫苗开发的前进之路。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-08-16 DOI: 10.1084/jem.20240002

Stephanie A Fritz, Juliane Bubeck Wardenburg

引用次数: 0

Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development. 胸腺中的自我调整：CD4与CD8血系的承诺和调节性T细胞的发育

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-07-09 DOI: 10.1084/jem.20230896

Isabel Baldwin, Ellen A Robey

引用次数: 0

Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance. 肿瘤细胞内在的Piezo2通过损害CD8+T细胞的干性维持来驱动放射抗性。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-08-21 DOI: 10.1084/jem.20231486

Naijun Miao, Dongqing Cao, Jingsi Jin, Guizhi Ma, Haihui Yu, Junwen Qu, Guiping Li, Caixia Gao, Dong Dong, Fan Xia, Wenwen Li

{"title":"Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance.","authors":"Naijun Miao, Dongqing Cao, Jingsi Jin, Guizhi Ma, Haihui Yu, Junwen Qu, Guiping Li, Caixia Gao, Dong Dong, Fan Xia, Wenwen Li","doi":"10.1084/jem.20231486","DOIUrl":"10.1084/jem.20231486","url":null,"abstract":"Changes in mechanosensitive ion channels following radiation have seldom been linked to therapeutic sensitivity or specific factors involved in antitumor immunity. Here, in this study, we found that the mechanical force sensor, Piezo2, was significantly upregulated in tumor cells after radiation, and Piezo2 knockout in tumor cells enhanced tumor growth suppression by radiotherapy. Specifically, loss of Piezo2 in tumor cells induced their IL-15 expression via unleashing JAK2/STAT1/IRF-1 axis after radiation. This increase in IL-15 activates IL-15Rα on tumor-infiltrating CD8+ T cells, thereby leading to their augmented effector and stem cell-like properties, along with reduced terminal exhausted feature. Importantly, Piezo2 expression was negatively correlated with CD8 infiltration, as well as with radiosensitivity of patients with rectum adenocarcinoma receiving radiotherapy treatment. Together, our findings reveal that tumor cell-intrinsic Piezo2 induces radioresistance by dampening the IRF-1/IL-15 axis, thus leading to impaired CD8+ T cell-dependent antitumor responses, providing insights into the further development of combination strategies to treat radioresistant cancers.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 10","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017685","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

Iron TAMs: The fallen protectors. 铁甲塔姆：堕落的保护者

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-09-30 DOI: 10.1084/jem.20240951

Lijuan Sun, Mikala Egeblad

引用次数: 0

SETD1B mutations confer apoptosis resistance and BCL2 independence in B cell lymphoma. SETD1B 突变使 B 细胞淋巴瘤具有抗凋亡性和 BCL2 独立性。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-09-05 DOI: 10.1084/jem.20231143

Ana Portelinha, Shenqiu Wang, Sara Parsa, Man Jiang, Alexander N Gorelick, Sagarajit Mohanty, Soumya Sharma, Elisa de Stanchina, Marjan Berishaj, Chunying Zhao, James Heward, Neeraj K Aryal, Omid Tavana, Jiayu Wen, Jude Fitzgibbon, Ahmet Dogan, Anas Younes, Ari M Melnick, Hans-Guido Wendel

{"title":"SETD1B mutations confer apoptosis resistance and BCL2 independence in B cell lymphoma.","authors":"Ana Portelinha, Shenqiu Wang, Sara Parsa, Man Jiang, Alexander N Gorelick, Sagarajit Mohanty, Soumya Sharma, Elisa de Stanchina, Marjan Berishaj, Chunying Zhao, James Heward, Neeraj K Aryal, Omid Tavana, Jiayu Wen, Jude Fitzgibbon, Ahmet Dogan, Anas Younes, Ari M Melnick, Hans-Guido Wendel","doi":"10.1084/jem.20231143","DOIUrl":"10.1084/jem.20231143","url":null,"abstract":"The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and 16% of diffuse large B cell lymphomas (DLBCL). Deficiency in SETD1B confers striking resistance to Venetoclax and an experimental MCL-1 inhibitor. SETD1B also acts as a tumor suppressor and cooperates with the loss of KMT2D in lymphoma development in vivo. Consistently, loss of SETD1B in human lymphomas typically coincides with loss of KMT2D. Mechanistically, SETD1B is required for the expression of several proapoptotic BCL2 family proteins. Conversely, inhibitors of the KDM5 histone H3K4 demethylases restore BIM and BIK expression and synergize with Venetoclax in SETD1B-deficient lymphomas. These results establish SETD1B as an epigenetic regulator of cell death and reveal a pharmacological strategy to augment Venetoclax sensitivity in lymphoma.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 10","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132924","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

Modeling memory B cell responses in a lymphoid organ-chip to evaluate mRNA vaccine boosting. 在淋巴器官芯片中模拟记忆性 B 细胞反应，以评估 mRNA 疫苗的增效作用。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-09-06 DOI: 10.1084/jem.20240289

Raphaël Jeger-Madiot, Delphine Planas, Isabelle Staropoli, Hippolyte Debarnot, Jérôme Kervevan, Héloïse Mary, Camilla Collina, Barbara F Fonseca, Rémy Robinot, Stacy Gellenoncourt, Olivier Schwartz, Lorna Ewart, Michael Bscheider, Samy Gobaa, Lisa A Chakrabarti

{"title":"Modeling memory B cell responses in a lymphoid organ-chip to evaluate mRNA vaccine boosting.","authors":"Raphaël Jeger-Madiot, Delphine Planas, Isabelle Staropoli, Hippolyte Debarnot, Jérôme Kervevan, Héloïse Mary, Camilla Collina, Barbara F Fonseca, Rémy Robinot, Stacy Gellenoncourt, Olivier Schwartz, Lorna Ewart, Michael Bscheider, Samy Gobaa, Lisa A Chakrabarti","doi":"10.1084/jem.20240289","DOIUrl":"10.1084/jem.20240289","url":null,"abstract":"Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a lymphoid organ-chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. Perfusion of the SARS-CoV-2 spike protein mimicked a vaccine boost by inducing a massive amplification of spike-specific memory B cells, plasmablast differentiation, and spike-specific antibody secretion. Features of lymphoid tissue, including the formation of activated CD4+ T cell/B cell clusters and the emigration of matured plasmablasts, were recapitulated in the LO chip. Importantly, myeloid cells were competent at capturing and expressing mRNA vectored by lipid nanoparticles, enabling the assessment of responses to mRNA vaccines. Comparison of on-chip responses to Wuhan monovalent and Wuhan/Omicron bivalent mRNA vaccine boosts showed equivalent induction of Omicron neutralizing antibodies, pointing at immune imprinting as reported in vivo. The LO chip thus represents a versatile platform suited to the preclinical evaluation of vaccine-boosting strategies.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 10","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140214","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

Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients. 中和 I 型 IFNs 的自身抗体是 10% 的重症蜱传脑炎患者的病因。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-09-24 DOI: 10.1084/jem.20240637

Adrian Gervais, Astrid Marchal, Andrea Fortova, Michaela Berankova, Lenka Krbkova, Martina Pychova, Jiri Salat, Shuxiang Zhao, Nacim Kerrouche, Tom Le Voyer, Karin Stiasny, Simon Raffl, Anne Schieber Pachart, Samira Fafi-Kremer, Simon Gravier, Davide F Robbiani, Laurent Abel, Margaret R MacDonald, Charles M Rice, Gaia Weissmann, Tarek Kamal Eldin, Eva Robatscher, Elke Maria Erne, Elisabetta Pagani, Alessandro Borghesi, Anne Puel, Paul Bastard, Aurélie Velay, Martin Martinot, Yves Hansmann, Judith H Aberle, Daniel Ruzek, Aurélie Cobat, Shen-Ying Zhang, Jean-Laurent Casanova

{"title":"Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients.","authors":"Adrian Gervais, Astrid Marchal, Andrea Fortova, Michaela Berankova, Lenka Krbkova, Martina Pychova, Jiri Salat, Shuxiang Zhao, Nacim Kerrouche, Tom Le Voyer, Karin Stiasny, Simon Raffl, Anne Schieber Pachart, Samira Fafi-Kremer, Simon Gravier, Davide F Robbiani, Laurent Abel, Margaret R MacDonald, Charles M Rice, Gaia Weissmann, Tarek Kamal Eldin, Eva Robatscher, Elke Maria Erne, Elisabetta Pagani, Alessandro Borghesi, Anne Puel, Paul Bastard, Aurélie Velay, Martin Martinot, Yves Hansmann, Judith H Aberle, Daniel Ruzek, Aurélie Cobat, Shen-Ying Zhang, Jean-Laurent Casanova","doi":"10.1084/jem.20240637","DOIUrl":"10.1084/jem.20240637","url":null,"abstract":"Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 10","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307869","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

Precursor central memory versus effector cell fate and naïve CD4+ T cell heterogeneity. 前体中央记忆细胞与效应细胞的命运以及幼稚 CD4+ T 细胞的异质性。

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-09-25 DOI: 10.1084/jem.20231193

Deeksha Deep, Herman Gudjonson, Chrysothemis C Brown, Samuel A Rose, Roshan Sharma, Yoselin A Paucar Iza, Seunghee Hong, Saskia Hemmers, Michail Schizas, Zhong-Min Wang, Yuezhou Chen, Duane R Wesemann, Virginia Pascual, Dana Pe'er, Alexander Y Rudensky

{"title":"Precursor central memory versus effector cell fate and naïve CD4+ T cell heterogeneity.","authors":"Deeksha Deep, Herman Gudjonson, Chrysothemis C Brown, Samuel A Rose, Roshan Sharma, Yoselin A Paucar Iza, Seunghee Hong, Saskia Hemmers, Michail Schizas, Zhong-Min Wang, Yuezhou Chen, Duane R Wesemann, Virginia Pascual, Dana Pe'er, Alexander Y Rudensky","doi":"10.1084/jem.20231193","DOIUrl":"10.1084/jem.20231193","url":null,"abstract":"Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage. Specifically, a previously unappreciated population of naïve CD4+ T cells sensing environmental type I IFN exhibited distinct activation thresholds, suggesting that naïve CD4+ T cell differentiation potential may be influenced by environmental cues. This population was expanded in human viral infection and type I IFN response-lined autoimmunity. Understanding the relevance of naïve T cell heterogeneity to beneficial and maladaptive T cell responses may have therapeutic implications for adoptive T cell therapies in cancer immunotherapy and vaccination.","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"221 10","pages":""},"PeriodicalIF":12.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347955","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

Generation and repair of thymic epithelial cells. 胸腺上皮细胞的生成与修复

IF 12.6 1区医学

Journal of Experimental Medicine Pub Date : 2024-10-07 Epub Date: 2024-07-09 DOI: 10.1084/jem.20230894

Graham Anderson, Emilie J Cosway, Kieran D James, Izumi Ohigashi, Yousuke Takahama

引用次数: 0