Science Immunology最新文献

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Immune signature clues are key to unlocking the mystery of clinical responses 免疫特征线索是解开临床反应之谜的关键
IF 16.3 1区 医学
Science Immunology Pub Date : 2025-08-01 DOI: 10.1126/sciimmunol.aea8733
Robin R. Kobylski, Laura A. Solt
{"title":"Immune signature clues are key to unlocking the mystery of clinical responses","authors":"Robin R. Kobylski,&nbsp;Laura A. Solt","doi":"10.1126/sciimmunol.aea8733","DOIUrl":"10.1126/sciimmunol.aea8733","url":null,"abstract":"<div >A gene signature predicts infection severity and all-cause mortality across risk factors modifiable with lifestyle changes and treatment.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 110","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758671","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
CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity CD4 T细胞疗法通过保持肠道屏障的完整性来抵消炎症和衰老
IF 16.3 1区 医学
Science Immunology Pub Date : 2025-08-01 DOI: 10.1126/sciimmunol.adv0985
Manuel M. Gómez de las Heras, Elisa Carrasco, Mario Pérez-Manrique, Naohiro Inohara, Sandra Delgado-Pulido, Álvaro Fernández-Almeida, María I. Gálvez-Castaño, Isaac Francos-Quijorna, Carolina Simó, Virginia García-Cañas, José Ignacio Escrig-Larena, Juan Francisco Aranda, Gonzalo Soto-Heredero, Enrique Gabandé-Rodríguez, Eva María Blanco, Joyce Días-Almeida, Gabriel Núñez, María Mittelbrunn
{"title":"CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity","authors":"Manuel M. Gómez de las Heras,&nbsp;Elisa Carrasco,&nbsp;Mario Pérez-Manrique,&nbsp;Naohiro Inohara,&nbsp;Sandra Delgado-Pulido,&nbsp;Álvaro Fernández-Almeida,&nbsp;María I. Gálvez-Castaño,&nbsp;Isaac Francos-Quijorna,&nbsp;Carolina Simó,&nbsp;Virginia García-Cañas,&nbsp;José Ignacio Escrig-Larena,&nbsp;Juan Francisco Aranda,&nbsp;Gonzalo Soto-Heredero,&nbsp;Enrique Gabandé-Rodríguez,&nbsp;Eva María Blanco,&nbsp;Joyce Días-Almeida,&nbsp;Gabriel Núñez,&nbsp;María Mittelbrunn","doi":"10.1126/sciimmunol.adv0985","DOIUrl":"10.1126/sciimmunol.adv0985","url":null,"abstract":"<div >Healthy aging relies on a symbiotic host-microbiota relationship. The age-associated decline of the immune system can pose a threat to this delicate equilibrium. In this work, we investigated how the functional deterioration of T cells can affect host-microbiota symbiosis and gut barrier integrity and the implications of this deterioration for inflammaging, senescence, and health decline. Using the <i>Tfam</i><sup>fl/fl</sup><i>Cd4</i><sup>Cre</sup> mouse model, we found that T cell failure compromised gut immunity leading to a decrease in T follicular cells and regulatory T cells (T<sub>reg</sub> cells) and an accumulation of highly proinflammatory and cytotoxic T cells. These alterations were associated with intestinal barrier disruption and gut dysbiosis. Microbiota depletion or adoptive transfer of total CD4 T cells or a T<sub>reg</sub> cell–enriched pool prevented gut barrier dysfunction and mitigated premature inflammaging and senescence, ultimately enhancing the health span in this mouse model. Thus, a competent CD4 T cell compartment is critical to ensure healthier aging by promoting host-microbiota mutualism and gut barrier integrity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 110","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adv0985","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756630","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
A LAGging kiss leaves T cells cold 滞后的吻会使T细胞变冷
IF 16.3 1区 医学
Science Immunology Pub Date : 2025-08-01 DOI: 10.1126/sciimmunol.aea8744
Thomas T. Xu, Shiv Pillai
{"title":"A LAGging kiss leaves T cells cold","authors":"Thomas T. Xu,&nbsp;Shiv Pillai","doi":"10.1126/sciimmunol.aea8744","DOIUrl":"10.1126/sciimmunol.aea8744","url":null,"abstract":"<div >LAG-3 dampens CD4+ T cell activation by disrupting CDε-Lck condensates and is a therapeutic target in both cancer and autoimmunity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 110","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758629","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
Vagal TRPV1+ sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics 迷走神经TRPV1 +感觉神经元通过调节肺髓细胞动力学来预防流感病毒感染
IF 16.3 1区 医学
Science Immunology Pub Date : 2025-08-01 DOI: 10.1126/sciimmunol.ads6243
Nicole Almanzar, Daping Yang, Jingya Xia, Swalpa Udit, Prabhu Joshi, Sandeep Adhikari, Daisy A. Hoagland, Stephen T. Yeung, Camille Khairallah, Tomas Huerta, Antonia Wallrapp, Benjamin D. Umans, Nicole Sarden, Ozge Erdogan, Nadia Baalbaki, Jiawei Hou, Anna Beekmayer-Dhillon, Juhyun Lee, Kimberly A. Meerschaert, Stephen D. Liberles, Ruth A. Franklin, Bryan G. Yipp, Kamal M. Khanna, Pankaj Baral, Adam L. Haber, Isaac M. Chiu
{"title":"Vagal TRPV1+ sensory neurons protect against influenza virus infection by regulating lung myeloid cell dynamics","authors":"Nicole Almanzar,&nbsp;Daping Yang,&nbsp;Jingya Xia,&nbsp;Swalpa Udit,&nbsp;Prabhu Joshi,&nbsp;Sandeep Adhikari,&nbsp;Daisy A. Hoagland,&nbsp;Stephen T. Yeung,&nbsp;Camille Khairallah,&nbsp;Tomas Huerta,&nbsp;Antonia Wallrapp,&nbsp;Benjamin D. Umans,&nbsp;Nicole Sarden,&nbsp;Ozge Erdogan,&nbsp;Nadia Baalbaki,&nbsp;Jiawei Hou,&nbsp;Anna Beekmayer-Dhillon,&nbsp;Juhyun Lee,&nbsp;Kimberly A. Meerschaert,&nbsp;Stephen D. Liberles,&nbsp;Ruth A. Franklin,&nbsp;Bryan G. Yipp,&nbsp;Kamal M. Khanna,&nbsp;Pankaj Baral,&nbsp;Adam L. Haber,&nbsp;Isaac M. Chiu","doi":"10.1126/sciimmunol.ads6243","DOIUrl":"10.1126/sciimmunol.ads6243","url":null,"abstract":"<div >Influenza viruses are a major global cause of morbidity and mortality. Although vagal TRPV1<sup>+</sup> nociceptive sensory neurons are known to mediate defenses against harmful agents, including pathogens, their function in lung antiviral defenses remains unclear. Our study demonstrates that both systemic and vagal-specific ablation of TRPV1<sup>+</sup> nociceptors reduce survival in mice infected with influenza A virus (IAV). Despite no difference in viral load, mice lacking TRPV1<sup>+</sup> neurons exhibited increased viral spread, exacerbated lung pathology, and elevated levels of proinflammatory cytokines. Loss of TRPV1<sup>+</sup> neurons altered the lung immune landscape, including an expansion of neutrophils and monocyte-derived macrophages. Transcriptional analysis revealed impaired interferon signaling in myeloid cells and an imbalance in distinct neutrophil subpopulations in the absence of nociceptors. Furthermore, antibody-mediated depletion of myeloid cells during IAV infection substantially improved survival after nociceptor ablation, underscoring the role of TRPV1<sup>+</sup> neurons in preventing pathogenic myeloid cell states that contribute to IAV-induced mortality.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 110","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ads6243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756483","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
Human CD4+ T cells regulate peripheral immune responses in rheumatoid arthritis via insulin-like growth factor–like family member 2 人CD4 + T细胞通过胰岛素样生长因子家族成员2调节类风湿关节炎的外周免疫反应
IF 16.3 1区 医学
Science Immunology Pub Date : 2025-08-01 DOI: 10.1126/sciimmunol.adr3838
Akinori Murakami, Rinko Akamine, Shiro Tanaka, Koichi Murata, Kohei Nishitani, Hiromu Ito, Ryu Watanabe, Takayuki Fujii, Takeshi Iwasaki, Yuki Masuo, Osamu Iri, Shinichiro Nakamura, Shinichi Kuriyama, Yugo Morita, Yasuhiro Murakawa, Chikashi Terao, Yukinori Okada, Motomu Hashimoto, Shuichi Matsuda, Hideki Ueno, Hiroyuki Yoshitomi
{"title":"Human CD4+ T cells regulate peripheral immune responses in rheumatoid arthritis via insulin-like growth factor–like family member 2","authors":"Akinori Murakami,&nbsp;Rinko Akamine,&nbsp;Shiro Tanaka,&nbsp;Koichi Murata,&nbsp;Kohei Nishitani,&nbsp;Hiromu Ito,&nbsp;Ryu Watanabe,&nbsp;Takayuki Fujii,&nbsp;Takeshi Iwasaki,&nbsp;Yuki Masuo,&nbsp;Osamu Iri,&nbsp;Shinichiro Nakamura,&nbsp;Shinichi Kuriyama,&nbsp;Yugo Morita,&nbsp;Yasuhiro Murakawa,&nbsp;Chikashi Terao,&nbsp;Yukinori Okada,&nbsp;Motomu Hashimoto,&nbsp;Shuichi Matsuda,&nbsp;Hideki Ueno,&nbsp;Hiroyuki Yoshitomi","doi":"10.1126/sciimmunol.adr3838","DOIUrl":"10.1126/sciimmunol.adr3838","url":null,"abstract":"<div >Human CD4<sup>+</sup> T cells play a central role in the pathogenesis of autoimmune diseases, but their immunoregulatory mechanisms driving pathogenesis remain to be elucidated. We show that human T peripheral helper cells (T<sub>PH</sub> cells) regulate peripheral immune responses via insulin-like growth factor–like family member 2 (IGFL2), an inflammatory factor found exclusively in primates. Single-cell RNA sequencing of seropositive rheumatoid arthritis (RA) synovium showed that <i>IGFL2</i> is specifically expressed by CD4<sup>+</sup> T cells, predominantly T<sub>PH</sub> cells. IGFL2 promotes transforming growth factor–β–induced CXCL13 production in CD4<sup>+</sup> T cells, activates nuclear factor κB signaling, and induces monocyte gene signatures like those of pathogenic macrophages. CRISPR-Cas9 knockout of IGFL2 in synovial T<sub>PH</sub> cells suppressed this gene signature in cocultured monocytes. Blood IGFL2 protein levels correlated with RA disease severity and could be used as a potential biomarker. These findings highlight the involvement of IGFL2 in RA pathogenesis, emphasizing how human T<sub>PH</sub> cells regulate local immune responses via IGFL2.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 110","pages":""},"PeriodicalIF":16.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756484","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
Regulatory T cells in brown adipose tissue safeguard thermogenesis by restraining interferon-γ–producing lymphocytes 褐色脂肪组织中的调节性T细胞通过抑制产生干扰素γ的淋巴细胞来保护产热
IF 17.6 1区 医学
Science Immunology Pub Date : 2025-07-25 DOI: 10.1126/sciimmunol.ads0478
Nathan W. Zammit, Ariana Vargas-Castillo, P. Kent Langston, Gang Wang, Yangzhong Zhou, Bruce M. Spiegelman, Christophe Benoist, Diane Mathis
{"title":"Regulatory T cells in brown adipose tissue safeguard thermogenesis by restraining interferon-γ–producing lymphocytes","authors":"Nathan W. Zammit,&nbsp;Ariana Vargas-Castillo,&nbsp;P. Kent Langston,&nbsp;Gang Wang,&nbsp;Yangzhong Zhou,&nbsp;Bruce M. Spiegelman,&nbsp;Christophe Benoist,&nbsp;Diane Mathis","doi":"10.1126/sciimmunol.ads0478","DOIUrl":"10.1126/sciimmunol.ads0478","url":null,"abstract":"<div >Whereas visceral adipose tissue (VAT) primarily stores excess energy, brown adipose tissue (BAT) dissipates it in a process termed nonshivering thermogenesis. Several key VAT features, particularly murine epidydimal VAT, are regulated by a distinct population of regulatory T (T<sub>reg</sub>) cells, raising the question of whether BAT hosts an analogous population. Although T<sub>reg</sub> cells have been observed in BAT, their properties and mechanisms of action require elucidation. We found BAT T<sub>reg</sub> cells to be heterogeneous in subtissular localization and subtype composition. Punctual depletion of T<sub>reg</sub> cells unleashed interferon-γ (IFN-γ)–producing lymphocytes in BAT, but not in subcutaneous or visceral fat depots, leading to IFN-γ–dependent mitochondrial dysfunction and metabolic dysregulation, thereby impeding nonshivering thermogenesis. Cold challenge selectively expanded the IL-18R1<sup>+</sup> T<sub>reg</sub> subtype in BAT; stripping this receptor specifically from T<sub>reg</sub> cells unleashed IFN-γ–producing lymphocytes and compromised temperature control. Thus, control of local IFN-γ production is a core feature of T<sub>reg</sub> cell control of tissue homeostasis.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 109","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ads0478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705732","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
Tissue origin and virus specificity shape human CD8+ T cell cytotoxicity 组织来源和病毒特异性决定了人CD8+ T细胞的细胞毒性
IF 17.6 1区 医学
Science Immunology Pub Date : 2025-07-18 DOI: 10.1126/sciimmunol.adq4881
Julia Niessl, Thomas R. Müller, Christian Constantz, Curtis Cai, Vera Nilsén, Olga Rivera Ballesteros, Sarah Adamo, Tobias Kammann, Elli Mouchtaridi, Yu Gao, Mily Akhirunnesa, Elisa J. M. Raineri, Whitney Weigel, Efthymia Kokkinou, Christopher Stamper, Anne Marchalot, John Bassett, Sabrina Ferreira, Inga Rodahl, Nicole Wild, Teresa Stellaccio, Demi Brownlie, Emma Ringqvist, Malin Flodström-Tullberg, Sian Llewellyn-Lacey, Chris Tibbitt, Quirin Hammer, Jakob Michaëlsson, David A. Price, Jenny Mjösberg, Nicole Marquardt, Johan K. Sandberg, Takuya Sekine, Carl Jorns, Marcus Buggert
{"title":"Tissue origin and virus specificity shape human CD8+ T cell cytotoxicity","authors":"Julia Niessl,&nbsp;Thomas R. Müller,&nbsp;Christian Constantz,&nbsp;Curtis Cai,&nbsp;Vera Nilsén,&nbsp;Olga Rivera Ballesteros,&nbsp;Sarah Adamo,&nbsp;Tobias Kammann,&nbsp;Elli Mouchtaridi,&nbsp;Yu Gao,&nbsp;Mily Akhirunnesa,&nbsp;Elisa J. M. Raineri,&nbsp;Whitney Weigel,&nbsp;Efthymia Kokkinou,&nbsp;Christopher Stamper,&nbsp;Anne Marchalot,&nbsp;John Bassett,&nbsp;Sabrina Ferreira,&nbsp;Inga Rodahl,&nbsp;Nicole Wild,&nbsp;Teresa Stellaccio,&nbsp;Demi Brownlie,&nbsp;Emma Ringqvist,&nbsp;Malin Flodström-Tullberg,&nbsp;Sian Llewellyn-Lacey,&nbsp;Chris Tibbitt,&nbsp;Quirin Hammer,&nbsp;Jakob Michaëlsson,&nbsp;David A. Price,&nbsp;Jenny Mjösberg,&nbsp;Nicole Marquardt,&nbsp;Johan K. Sandberg,&nbsp;Takuya Sekine,&nbsp;Carl Jorns,&nbsp;Marcus Buggert","doi":"10.1126/sciimmunol.adq4881","DOIUrl":"10.1126/sciimmunol.adq4881","url":null,"abstract":"<div >CD8<sup>+</sup> T cells are classically defined by cytotoxic activity, but it has remained unclear whether cytotoxic programs are compartmentalized across tissues and memory subsets. Here, we established a human organ donor cohort and found that expression of conventional cytotoxic molecules—granulysin, perforin, and granzyme B—was most prominent among circulating memory CD8<sup>+</sup> T cells and decreased progressively with tissue residency, inversely mirroring the expression of CD69 and CD103. Other cytotoxic molecules, including granzymes A, H, K, and M, were variably expressed across tissues, and memory CD8<sup>+</sup> T cells targeting persistent viruses expressed multiple granzymes coordinately. In an in vitro tonsil system, transforming growth factor–β induced discordant regulation of cytotoxic molecules and CD103. Combined with interleukin-15, this circuitry modulated proliferation and the acquisition of redirected killing activity via perforin and granzyme B. Our findings suggest that human memory CD8<sup>+</sup> T cell cytotoxicity is intricately regulated by environmental cues reflecting tissue location and antigen specificity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 109","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657797","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
Interactions between placental Hofbauer cells and L. monocytogenes change throughout gestation 胎盘霍夫鲍尔细胞与单核增生乳杆菌之间的相互作用在整个妊娠期发生变化
IF 17.6 1区 医学
Science Immunology Pub Date : 2025-07-18 DOI: 10.1126/sciimmunol.adq3066
Nagisa Yoshida, Anna Appios, Qian Li, Joseph P. Hutton, George Wood, Martin Potts, Julia Aleksandrowicz, Enrico R. Barrozo, Freya Dover, Holly Anderson, Katie Stephens, Irving L. M. H. Aye, Jake R. Thomas, Hannah C. M. Schenk, Adam M. Bourke, Catherine E. Aiken, Ashley Moffett, Andrew Sharkey, Anna V. Protasio, Kjersti M. Aagaard, James R. Edgar, Betty Y. W. Chung, Naomi McGovern
{"title":"Interactions between placental Hofbauer cells and L. monocytogenes change throughout gestation","authors":"Nagisa Yoshida,&nbsp;Anna Appios,&nbsp;Qian Li,&nbsp;Joseph P. Hutton,&nbsp;George Wood,&nbsp;Martin Potts,&nbsp;Julia Aleksandrowicz,&nbsp;Enrico R. Barrozo,&nbsp;Freya Dover,&nbsp;Holly Anderson,&nbsp;Katie Stephens,&nbsp;Irving L. M. H. Aye,&nbsp;Jake R. Thomas,&nbsp;Hannah C. M. Schenk,&nbsp;Adam M. Bourke,&nbsp;Catherine E. Aiken,&nbsp;Ashley Moffett,&nbsp;Andrew Sharkey,&nbsp;Anna V. Protasio,&nbsp;Kjersti M. Aagaard,&nbsp;James R. Edgar,&nbsp;Betty Y. W. Chung,&nbsp;Naomi McGovern","doi":"10.1126/sciimmunol.adq3066","DOIUrl":"10.1126/sciimmunol.adq3066","url":null,"abstract":"<div >Hofbauer cells (HBCs) are extraembryonic macrophages generated de novo within the human placenta. In this study, we explored how the properties of HBCs change throughout gestation. Our analysis revealed transcriptomic differences between first-trimester and term HBCs, with many of the altered genes linked to immune responses. As pregnancy progresses, HBCs exhibit a marked decrease in phagosome maturation and acidification. We show that the differences between first-trimester and term HBCs are important in the context of infection with <i>Listeria monocytogenes</i>, a pathogen that crosses the placenta and replicates within macrophages. Specifically, we observed reduced colony-forming units and diminished actin recruitment by <i>L. monocytogenes</i> in first-trimester HBCs compared with term HBCs. Our findings indicate that the ability of <i>L. monocytogenes</i> to escape from vacuoles is impaired within first-trimester HBCs. Thus, the changes in HBC biology across pregnancy are important in shaping their interactions with <i>L. monocytogenes.</i></div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 109","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adq3066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657779","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
OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation OTUD3通过抑制微生物介导的STING激活来预防溃疡性结肠炎
IF 17.6 1区 医学
Science Immunology Pub Date : 2025-07-18 DOI: 10.1126/sciimmunol.adm6843
Bo Li, Taiki Sakaguchi, Haruka Tani, Takayoshi Ito, Mari Murakami, Ryu Okumura, Masao Kobayashi, Daisuke Okuzaki, Daisuke Motooka, Hiroki Ikeuchi, Takayuki Ogino, Tsunekazu Mizushima, Seiichi Hirota, Yuriko Otake-Kasamoto, Toshihiro Kishikawa, Shota Nakamura, Kouji Kobiyama, Ken J. Ishii, Takao Hashiguchi, Taro Kawai, Etsushi Kuroda, Shinichiro Shinzaki, Wataru Ise, Tomohiro Kurosaki, Akira Kikuchi, Yoshihiko Tomofuji, Yukinori Okada, Kiyoshi Takeda, Hisako Kayama
{"title":"OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation","authors":"Bo Li,&nbsp;Taiki Sakaguchi,&nbsp;Haruka Tani,&nbsp;Takayoshi Ito,&nbsp;Mari Murakami,&nbsp;Ryu Okumura,&nbsp;Masao Kobayashi,&nbsp;Daisuke Okuzaki,&nbsp;Daisuke Motooka,&nbsp;Hiroki Ikeuchi,&nbsp;Takayuki Ogino,&nbsp;Tsunekazu Mizushima,&nbsp;Seiichi Hirota,&nbsp;Yuriko Otake-Kasamoto,&nbsp;Toshihiro Kishikawa,&nbsp;Shota Nakamura,&nbsp;Kouji Kobiyama,&nbsp;Ken J. Ishii,&nbsp;Takao Hashiguchi,&nbsp;Taro Kawai,&nbsp;Etsushi Kuroda,&nbsp;Shinichiro Shinzaki,&nbsp;Wataru Ise,&nbsp;Tomohiro Kurosaki,&nbsp;Akira Kikuchi,&nbsp;Yoshihiko Tomofuji,&nbsp;Yukinori Okada,&nbsp;Kiyoshi Takeda,&nbsp;Hisako Kayama","doi":"10.1126/sciimmunol.adm6843","DOIUrl":"10.1126/sciimmunol.adm6843","url":null,"abstract":"<div >Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are believed to play crucial roles in the pathogenesis of UC, but the influence of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remains poorly understood. Here, we demonstrate that OTU deubiquitinase 3 (OTUD3) suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3′3’-cGAMP) in the colon by deubiquitinating stimulator of interferon genes (STING). Mice harboring a UC risk missense variant in the <i>Otud3</i> gene showed pathological features of UC in the colon after transplantation of a fecal microbiota with the potential to produce excessive cGAMP from patients with UC. Collectively, these results highlight a mechanism of the interaction between OTUD3 in host fibroblasts and STING-activating microbiota in UC development.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"10 109","pages":""},"PeriodicalIF":17.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144657759","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
Noncanonical Hedgehog signaling through Smoothened controls cytotoxic T cell migration in the tumor microenvironment 非规范Hedgehog信号通过Smoothened控制肿瘤微环境中细胞毒性T细胞的迁移
IF 17.6 1区 医学
Science Immunology Pub Date : 2025-07-11 DOI: 10.1126/sciimmunol.adr3127
Chrysa Kapeni, Louise O’Brien, Dilyara Sabirova, Oliver Cast, Valentina Carbonaro, Stephen Clark-Leonard, Anne C. Machel, Flavio Beke, Sarah McDonald, Kate Fife, Maike de la Roche
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