Science Immunology最新文献

Erratum for the Research Article “Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis” 研究文章“单细胞谱揭示溃疡性结肠炎中不同的γδ T细胞亚群”的勘误

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-08

引用次数: 0

Monocyte-derived macrophages drive neurological tissue damage through mitochondrial reactive oxygen species 单核细胞来源的巨噬细胞通过线粒体活性氧驱动神经组织损伤

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-08

Juan Villar-Vesga, Donatella De Feo, Pauline Clément, Viola Bugada, Elèni Meuffels, Hannah Van Hove, Mitchell Bijnen, James King, Sophie Grundschober, Can Ulutekin, Maria Pena-Francesch, Sara Costa-Pereira, Laura Oberbichler, Violetta Gogoleva, Jeanne Kim, Katarina Wendy Schmidt, Musadiq A. Bhat, Deborah Greis, Frauke Seehusen, Francesco Prisco, Urvashi Dalvi, Dietmar Benke, Bettina Schreiner, Tommaso Patriachi, Florian Ingelfinger, Isabelle C. Arnold, Christian Münz, Melanie Greter, Aiman S. Saab, Burkhard Becher, Sarah Mundt

{"title":"Monocyte-derived macrophages drive neurological tissue damage through mitochondrial reactive oxygen species","authors":"Juan Villar-Vesga, Donatella De Feo, Pauline Clément, Viola Bugada, Elèni Meuffels, Hannah Van Hove, Mitchell Bijnen, James King, Sophie Grundschober, Can Ulutekin, Maria Pena-Francesch, Sara Costa-Pereira, Laura Oberbichler, Violetta Gogoleva, Jeanne Kim, Katarina Wendy Schmidt, Musadiq A. Bhat, Deborah Greis, Frauke Seehusen, Francesco Prisco, Urvashi Dalvi, Dietmar Benke, Bettina Schreiner, Tommaso Patriachi, Florian Ingelfinger, Isabelle C. Arnold, Christian Münz, Melanie Greter, Aiman S. Saab, Burkhard Becher, Sarah Mundt","doi":"","DOIUrl":"","url":null,"abstract":"<div >Reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs) are widely believed to drive tissue damage in multiple sclerosis (MS), yet the distinct roles of central nervous system (CNS)–resident versus CNS-invading MPs remain unclear. Here, we combined single-cell profiling and conditional gene targeting to map and modulate ROS production across CNS MPs in a preclinical mouse model of MS. We show that monocyte-derived macrophages (MdMs) exhibit a higher oxidative stress gene signature and produce more ROS than microglia (Mglia). Challenging previous assumptions, our findings reveal that phagocytic NADPH oxidase 2 is dispensable for neuroinflammation. In contrast, quenching mitochondrial ROS (mtROS) through mitochondria-targeted catalase (mCAT) expression in MdMs, but not in Mglia, ameliorated disease severity in acute neuroinflammation. Although core phagocyte functions were unaltered in mCAT-expressing MdMs, our results demonstrate a direct neurotoxic role of mtROS. In sum, we identify MdMs as the primary driver of ROS-mediated oxidative neurological tissue damage.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830229","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

Monocyte-derived macrophages drive neurological tissue damage through mitochondrial reactive oxygen species. 单核细胞来源的巨噬细胞通过线粒体活性氧驱动神经组织损伤。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-08 DOI: 10.1126/sciimmunol.adw5197

Juan Villar-Vesga, Donatella De Feo, Pauline Clément, Viola Bugada, Elèni Meuffels, Hannah Van Hove, Mitchell Bijnen, James King, Sophie Grundschober, Can Ulutekin, Maria Pena-Francesch, Sara Costa-Pereira, Laura Oberbichler, Violetta Gogoleva, Jeanne Kim, Katarina Wendy Schmidt, Musadiq A Bhat, Deborah Greis, Frauke Seehusen, Francesco Prisco, Urvashi Dalvi, Dietmar Benke, Bettina Schreiner, Tommaso Patriachi, Florian Ingelfinger, Isabelle C Arnold, Christian Münz, Melanie Greter, Aiman S Saab, Burkhard Becher, Sarah Mundt

{"title":"Monocyte-derived macrophages drive neurological tissue damage through mitochondrial reactive oxygen species.","authors":"Juan Villar-Vesga, Donatella De Feo, Pauline Clément, Viola Bugada, Elèni Meuffels, Hannah Van Hove, Mitchell Bijnen, James King, Sophie Grundschober, Can Ulutekin, Maria Pena-Francesch, Sara Costa-Pereira, Laura Oberbichler, Violetta Gogoleva, Jeanne Kim, Katarina Wendy Schmidt, Musadiq A Bhat, Deborah Greis, Frauke Seehusen, Francesco Prisco, Urvashi Dalvi, Dietmar Benke, Bettina Schreiner, Tommaso Patriachi, Florian Ingelfinger, Isabelle C Arnold, Christian Münz, Melanie Greter, Aiman S Saab, Burkhard Becher, Sarah Mundt","doi":"10.1126/sciimmunol.adw5197","DOIUrl":"https://doi.org/10.1126/sciimmunol.adw5197","url":null,"abstract":"Reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs) are widely believed to drive tissue damage in multiple sclerosis (MS), yet the distinct roles of central nervous system (CNS)-resident versus CNS-invading MPs remain unclear. Here, we combined single-cell profiling and conditional gene targeting to map and modulate ROS production across CNS MPs in a preclinical mouse model of MS. We show that monocyte-derived macrophages (MdMs) exhibit a higher oxidative stress gene signature and produce more ROS than microglia (Mglia). Challenging previous assumptions, our findings reveal that phagocytic NADPH oxidase 2 is dispensable for neuroinflammation. In contrast, quenching mitochondrial ROS (mtROS) through mitochondria-targeted catalase (mCAT) expression in MdMs, but not in Mglia, ameliorated disease severity in acute neuroinflammation. Although core phagocyte functions were unaltered in mCAT-expressing MdMs, our results demonstrate a direct neurotoxic role of mtROS. In sum, we identify MdMs as the primary driver of ROS-mediated oxidative neurological tissue damage.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":"eadw5197"},"PeriodicalIF":16.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856941","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

In vivo reprogramming of cytotoxic effector CD8 T cells via fractalkine-conjugated mRNA-LNPs. 通过分形因子偶联mRNA-LNPs在体内重编程细胞毒性效应CD8 T细胞。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-08 DOI: 10.1126/sciimmunol.aec3436

Angela R Corrigan, Shin Foong Ngiow, Maura Statzu, Amie Albertus, M Betina Pampena, Jayme M L Nordin, Stephen D Carro, Justin Harper, Rachelle L Stammen, Jennifer Wood, Houping Ni, Justin Su, Marziyeh Hajialyani, Vladimir V Shuvaev, Victor Alcalde, Mohammed-Alkhatim A Ali, Jacob T Hamilton, Rajesvaran Ramalingam, Vincent H Wu, Mirko Paiardini, Drew Weissman, E John Wherry, Edward F Kreider, Michael R Betts

{"title":"In vivo reprogramming of cytotoxic effector CD8 T cells via fractalkine-conjugated mRNA-LNPs.","authors":"Angela R Corrigan, Shin Foong Ngiow, Maura Statzu, Amie Albertus, M Betina Pampena, Jayme M L Nordin, Stephen D Carro, Justin Harper, Rachelle L Stammen, Jennifer Wood, Houping Ni, Justin Su, Marziyeh Hajialyani, Vladimir V Shuvaev, Victor Alcalde, Mohammed-Alkhatim A Ali, Jacob T Hamilton, Rajesvaran Ramalingam, Vincent H Wu, Mirko Paiardini, Drew Weissman, E John Wherry, Edward F Kreider, Michael R Betts","doi":"10.1126/sciimmunol.aec3436","DOIUrl":"https://doi.org/10.1126/sciimmunol.aec3436","url":null,"abstract":"Selective in vivo reprogramming of cytotoxic effector CD8 T (Teff) cells holds tremendous promise as a therapeutic tool but has not yet been accomplished. Here, we demonstrate that fractalkine-conjugated mRNA lipid nanoparticles (mRNA-LNPs) can specifically target and deliver mRNA to CX3CR1+ Teff cells in vitro and in vivo. In mice, fractalkine-conjugated mRNA-LNPs targeted up to 95% of blood and splenic Teff cells. In addition, delivery of IL-2-encoding mRNA and human CD62L-encoding mRNA to mouse Teff cells enabled robust exogenous IL-2 secretion and CD62L expression. In rhesus macaques, fractalkine-conjugated mRNA-LNPs targeted up to ~100% of peripheral blood Teff cells, and delivery of human CD62L-encoding mRNA enabled cell-surface human CD62L expression on peripheral blood Teff cells and detection of human CD62L+ Teff cells in lymphoid tissue. Collectively, these data demonstrate the potential of natural receptor ligand-based targeting of mRNA-LNPs for rapid, efficient, and transient in vivo modification of Teff cells.","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":"eaec3436"},"PeriodicalIF":16.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857000","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

In vivo reprogramming of cytotoxic effector CD8 T cells via fractalkine-conjugated mRNA-LNPs 通过分形因子偶联mRNA-LNPs在体内重编程细胞毒性效应CD8 T细胞

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-08

Angela R. Corrigan, Shin Foong Ngiow, Maura Statzu, Amie Albertus, M. Betina Pampena, Jayme M. L. Nordin, Stephen D. Carro, Justin Harper, Rachelle L. Stammen, Jennifer Wood, Houping Ni, Justin Su, Marziyeh Hajialyani, Vladimir V. Shuvaev, Victor Alcalde, Mohammed-Alkhatim A. Ali, Jacob T. Hamilton, Rajesvaran Ramalingam, Vincent H. Wu, Mirko Paiardini, Drew Weissman, E. John Wherry, Edward F. Kreider, Michael R. Betts

{"title":"In vivo reprogramming of cytotoxic effector CD8 T cells via fractalkine-conjugated mRNA-LNPs","authors":"Angela R. Corrigan, Shin Foong Ngiow, Maura Statzu, Amie Albertus, M. Betina Pampena, Jayme M. L. Nordin, Stephen D. Carro, Justin Harper, Rachelle L. Stammen, Jennifer Wood, Houping Ni, Justin Su, Marziyeh Hajialyani, Vladimir V. Shuvaev, Victor Alcalde, Mohammed-Alkhatim A. Ali, Jacob T. Hamilton, Rajesvaran Ramalingam, Vincent H. Wu, Mirko Paiardini, Drew Weissman, E. John Wherry, Edward F. Kreider, Michael R. Betts","doi":"","DOIUrl":"","url":null,"abstract":"<div >Selective in vivo reprogramming of cytotoxic effector CD8 T (Teff) cells holds tremendous promise as a therapeutic tool but has not yet been accomplished. Here, we demonstrate that fractalkine-conjugated mRNA lipid nanoparticles (mRNA-LNPs) can specifically target and deliver mRNA to CX3CR1+ Teff cells in vitro and in vivo. In mice, fractalkine-conjugated mRNA-LNPs targeted up to 95% of blood and splenic Teff cells. In addition, delivery of IL-2–encoding mRNA and human CD62L-encoding mRNA to mouse Teff cells enabled robust exogenous IL-2 secretion and CD62L expression. In rhesus macaques, fractalkine-conjugated mRNA-LNPs targeted up to ~100% of peripheral blood Teff cells, and delivery of human CD62L-encoding mRNA enabled cell-surface human CD62L expression on peripheral blood Teff cells and detection of human CD62L+ Teff cells in lymphoid tissue. Collectively, these data demonstrate the potential of natural receptor ligand-based targeting of mRNA-LNPs for rapid, efficient, and transient in vivo modification of Teff cells.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830231","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

Erratum for the Research Article "Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis". 研究文章“单细胞谱揭示溃疡性结肠炎中不同的γδ T细胞亚群”的勘误。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-08 DOI: 10.1126/sciimmunol.aeh9584

引用次数: 0

A parasite partner for regulatory affairs 监管事务的寄生伙伴。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-01 DOI: 10.1126/sciimmunol.aei2411

Isabella O. Conway, Christopher A. Hunter

引用次数: 0

B cells gone broad: A deep dive into SARS-CoV-2 antibody breadth B细胞变宽：深入研究SARS-CoV-2抗体的广度。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-01 DOI: 10.1126/sciimmunol.aei2832

Easton E. Ford, Melissa L. Smith

引用次数: 0

Foxp3 drives context-dependent epigenetic programs that define regulatory T cell molecular identity and function Foxp3驱动上下文依赖的表观遗传程序，定义调节性T细胞分子身份和功能。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-01 DOI: 10.1126/sciimmunol.aed2111

Yuxi Wei, Hinako Ago, Ryuichi Murakami, Shotaro Funatsu, Marina Osaki, Akira Nakajima, Yoshinori Hasegawa, Ryoji Kawakami, Shimon Sakaguchi, Shohei Hori

{"title":"Foxp3 drives context-dependent epigenetic programs that define regulatory T cell molecular identity and function","authors":"Yuxi Wei, Hinako Ago, Ryuichi Murakami, Shotaro Funatsu, Marina Osaki, Akira Nakajima, Yoshinori Hasegawa, Ryoji Kawakami, Shimon Sakaguchi, Shohei Hori","doi":"10.1126/sciimmunol.aed2111","DOIUrl":"10.1126/sciimmunol.aed2111","url":null,"abstract":"<div >Regulatory T cells (Treg cells) express the master regulator, Foxp3, and display distinctive epigenetic landscapes ensuring Treg cell–specific gene expression and stable suppressive functions, yet Foxp3’s contribution to this epigenetic identity remains unclear. Leveraging Foxp3-transduced conventional T cells as a gain-of-function probe in mice, we identified a previously unrecognized subset that acquires endogenous Foxp3 expression, Treg cell–like transcriptomic and chromatin features, and suppressive functions exclusively in vivo. These Foxp3-driven features were conserved in Treg cells but impaired in Foxp3-mutant Treg-like cells, demonstrating a Foxp3 requirement. Induction of endogenous Foxp3 expression in vivo required reduced AKT-mTOR signaling and Foxp3-dependent engagement of STAT5 and nuclear factor κB (NF-κB). Temporal chromatin profiling revealed stepwise Foxp3-driven regulatory programs, including a core program shared across Treg cell subsets and effector-specific programs, both associated with NF-κB activity and Foxp3 binding. Thus, Foxp3 integrates cell-intrinsic and environmental contexts to drive epigenetic programs defining Treg cell identities and functions, with implications for Foxp3-based therapies.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147820521","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

Foxp3: The epigenetic engineer of regulatory T cell identity Foxp3：调控T细胞身份的表观遗传工程。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-01 DOI: 10.1126/sciimmunol.aeg4759

Mieke Metzemaekers, Ralph Stadhouders

引用次数: 0