Science Immunology最新文献_第2页

Gastrointestinal germinal center B cell depletion and reduction in IgA+ plasma cells in HIV-1 infection 胃肠道生殖中心 B 细胞耗竭和 HIV-1 感染者 IgA + 浆细胞减少

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Science Immunology Pub Date : 2024-10-25 DOI: 10.1126/sciimmunol.ado0090

Francesca Cossarini, Joan Shang, Azra Krek, Zainab Al-Taie, Ruixue Hou, Pablo Canales-Herrerias, Minami Tokuyama, Michael Tankelevich, Adam Tillowitz, Divya Jha, Alexandra E. Livanos, Louise Leyre, Mathieu Uzzan, Gustavo Martinez-Delgado, Matthew D. Taylor, Keshav Sharma, Arno R. Bourgonje, Michael Cruz, Giorgio Ioannou, Travis Dawson, Darwin D''Souza, Seunghee Kim-Schulze, Ahmed Akm, Judith A. Aberg, Benjamin K. Chen, Douglas S. Kwon, Sacha Gnjatic, Alexandros D. Polydorides, Andrea Cerutti, Carmen Argmann, Ivan Vujkovic-Cvijin, Mayte Suarez-Fariñas, Francesca Petralia, Jeremiah J. Faith, Saurabh Mehandru

{"title":"Gastrointestinal germinal center B cell depletion and reduction in IgA+ plasma cells in HIV-1 infection","authors":"Francesca Cossarini, Joan Shang, Azra Krek, Zainab Al-Taie, Ruixue Hou, Pablo Canales-Herrerias, Minami Tokuyama, Michael Tankelevich, Adam Tillowitz, Divya Jha, Alexandra E. Livanos, Louise Leyre, Mathieu Uzzan, Gustavo Martinez-Delgado, Matthew D. Taylor, Keshav Sharma, Arno R. Bourgonje, Michael Cruz, Giorgio Ioannou, Travis Dawson, Darwin D''Souza, Seunghee Kim-Schulze, Ahmed Akm, Judith A. Aberg, Benjamin K. Chen, Douglas S. Kwon, Sacha Gnjatic, Alexandros D. Polydorides, Andrea Cerutti, Carmen Argmann, Ivan Vujkovic-Cvijin, Mayte Suarez-Fariñas, Francesca Petralia, Jeremiah J. Faith, Saurabh Mehandru","doi":"10.1126/sciimmunol.ado0090","DOIUrl":"10.1126/sciimmunol.ado0090","url":null,"abstract":"<div >Gastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high-resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. Immunoglobulin A–positive (IgA<sup>+</sup>) PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)–treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 100","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ado0090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489635","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}

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Erratum for the Research Article “Initiator cell death event induced by SARS-CoV-2 in the human airway epithelium” by K. Liang et al. 对 K. Liang 等人的研究文章 "SARS-CoV-2 在人气道上皮细胞中诱导的启动子细胞死亡事件 "的勘误

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Science Immunology Pub Date : 2024-10-18 DOI: 10.1126/sciimmunol.adt4547

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Erratum for the Research Article “Circulating KLRG1+ long-lived effector memory T cells retain the flexibility to become tissue resident” by E. D. Lucas et al. E. D. Lucas 等人的研究文章 "循环中的 KLRG1+ 长效记忆 T 细胞具有成为组织常驻细胞的灵活性 "的勘误。

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Science Immunology Pub Date : 2024-10-18 DOI: 10.1126/sciimmunol.adt4549

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Programmable bacteria synergize with PD-1 blockade to overcome cancer cell–intrinsic immune resistance mechanisms 可编程细菌与 PD-1 阻断剂协同作用，克服癌细胞内在的免疫抵抗机制

IF 17.6 1区医学

Science Immunology Pub Date : 2024-10-18 DOI: 10.1126/sciimmunol.adn9879

Fangda Li, Zaofeng Yang, Thomas M. Savage, Rosa L. Vincent, Kenia de los Santos-Alexis, Alexander Ahn, Mathieu Rouanne, Dylan L. Mariuzza, Tal Danino, Nicholas Arpaia

{"title":"Programmable bacteria synergize with PD-1 blockade to overcome cancer cell–intrinsic immune resistance mechanisms","authors":"Fangda Li, Zaofeng Yang, Thomas M. Savage, Rosa L. Vincent, Kenia de los Santos-Alexis, Alexander Ahn, Mathieu Rouanne, Dylan L. Mariuzza, Tal Danino, Nicholas Arpaia","doi":"10.1126/sciimmunol.adn9879","DOIUrl":"10.1126/sciimmunol.adn9879","url":null,"abstract":"<div >Interferon-γ (IFN-γ) is a potent cytokine critical for response to immunotherapy, yet conventional methods to systemically deliver this cytokine have been hindered by severe dose-limiting toxicities. Here, we engineered a strain of probiotic bacteria that home to tumors and locally release IFN-γ. A single intratumoral injection of these IFN-γ–producing bacteria was sufficient to drive systemic tumor antigen–specific antitumor immunity, without observable toxicity. Although cancer cells use various resistance mechanisms to evade immune responses, bacteria-derived IFN-γ overcame primary resistance to programmed cell death 1 (PD-1) blockade via activation of cytotoxic Foxp3<sup>−</sup>CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Moreover, by activating natural killer (NK) cells, bacteria-derived IFN-γ also overcame acquired resistance mechanisms to PD-1 blockade, specifically loss-of-function mutations in IFN-γ signaling and antigen presentation pathways. Collectively, these results demonstrate the promise of combining IFN-γ–producing bacteria with PD-1 blockade as a therapeutic strategy for overcoming immunotherapy-resistant, locally advanced, and metastatic disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 100","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adn9879","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449590","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}

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The acid-sensing receptor GPR65 on tumor macrophages drives tumor growth in obesity 肿瘤巨噬细胞上的酸感应受体 GPR65 推动肥胖症肿瘤的生长

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Science Immunology Pub Date : 2024-10-18 DOI: 10.1126/sciimmunol.adg6453

Sreya Bagchi, Robert Yuan, Han-Li Huang, Weiruo Zhang, David Kung-Chun Chiu, Hyungjoo Kim, Sophia L. Cha, Lorna Tolentino, Joshua Lowitz, Yilin Liu, Anna Moshnikova, Oleg Andreev, Sylvia Plevritis, Edgar G. Engleman

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An ILC2-chitinase circuit restores lung homeostasis after epithelial injury 上皮损伤后，ILC2-几丁质酶回路可恢复肺稳态

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Science Immunology Pub Date : 2024-10-18 DOI: 10.1126/sciimmunol.adl2986

Haerin Jung, Do-Hyun Kim, Roberto Efraín Díaz, J. Michael White, Summer Rucknagel, Lauryn Mosby, Yilin Wang, Sanjana Reddy, Emma S. Winkler, Ahmed O. Hassan, Baoling Ying, Michael S. Diamond, Richard M. Locksley, James S. Fraser, Steven J. Van Dyken

{"title":"An ILC2-chitinase circuit restores lung homeostasis after epithelial injury","authors":"Haerin Jung, Do-Hyun Kim, Roberto Efraín Díaz, J. Michael White, Summer Rucknagel, Lauryn Mosby, Yilin Wang, Sanjana Reddy, Emma S. Winkler, Ahmed O. Hassan, Baoling Ying, Michael S. Diamond, Richard M. Locksley, James S. Fraser, Steven J. Van Dyken","doi":"10.1126/sciimmunol.adl2986","DOIUrl":"10.1126/sciimmunol.adl2986","url":null,"abstract":"<div >Environmental exposures increase the risk for severe lung disease, but specific drivers of persistent epithelial injury and immune dysfunction remain unclear. Here, we identify a feedback circuit triggered by chitin, a common component of airborne particles, that affects lung health after epithelial injury. In mice, epithelial damage disrupts lung chitinase activity, leading to environmental chitin accumulation, impaired epithelial renewal, and group 2 innate lymphoid cell (ILC2) activation. ILC2s, in turn, restore homeostasis by inducing acidic mammalian chitinase (AMCase) in regenerating epithelial cells and promoting chitin degradation, epithelial differentiation, and inflammatory resolution. Mice lacking AMCase or ILC2s fail to clear chitin and exhibit increased mortality and impaired epithelial regeneration after injury. These effects are ameliorated by chitinase replacement therapy, demonstrating that chitin degradation is crucial for recovery after various forms of lung perturbation. Thus, the ILC2-chitinase response circuit may serve as a target for alleviating persistent postinjury lung epithelial and immune dysfunction.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 100","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449594","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}

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Contactin-4 suppresses antitumor T cell responses by engaging amyloid precursor protein 接触素-4通过与淀粉样前体蛋白结合抑制抗肿瘤 T 细胞反应

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Science Immunology Pub Date : 2024-10-11 DOI: 10.1126/sciimmunol.adk7237

Bu-Nam Jeon, Sujeong Kim, Yunjae Kim, Hyunkyung Yu, Changho Park, Gihyeon Kim, Youngeun Ha, Gyeong-yeon Kim, Hyunuk Kim, Karolina A. Palucka, Charles Lee, Miyoung Cha, Hansoo Park

{"title":"Contactin-4 suppresses antitumor T cell responses by engaging amyloid precursor protein","authors":"Bu-Nam Jeon, Sujeong Kim, Yunjae Kim, Hyunkyung Yu, Changho Park, Gihyeon Kim, Youngeun Ha, Gyeong-yeon Kim, Hyunuk Kim, Karolina A. Palucka, Charles Lee, Miyoung Cha, Hansoo Park","doi":"10.1126/sciimmunol.adk7237","DOIUrl":"10.1126/sciimmunol.adk7237","url":null,"abstract":"<div >Immune checkpoint inhibitors have substantial advanced tumor treatment, but their limited benefits and strong responses in only a subset of patients remain challenging. In this study, we explored the immunomodulatory function of contactin-4 (CNTN4). CNTN4 was highly expressed in tumor tissues, and expression impaired the antitumor function of T cells. CNTN4 bound to amyloid precursor protein (APP) on T cells, which attenuated conjugation between cancer cells and T cells, and diminished T cell receptor signaling cascades. We developed an anti-CNTN4 antibody (GENA-104A16) and an anti-APP antibody (5A7) that blocked the binding between CNTN4 and APP. Administration of either GENA-104A16 or 5A7 promoted antitumor T cell responses in a syngeneic mouse model and increased tumor-infiltrating lymphocytes in vivo. Furthermore, elevated CNTN4 levels were associated with poor prognosis and negatively correlated with various cytotoxic immune-related markers. These results suggest that CNTN4-APP is an inhibitory checkpoint in T cells and represents a promising therapeutic strategy for cancer immunotherapy.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 100","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406787","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}

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Human cytomegalovirus UL18 prevents priming of MHC-E– and MHC-II–restricted CD8+ T cells 人类巨细胞病毒 UL18 可阻止 MHC-E 和 MHC-II 限制性 CD8+ T 细胞的启动。

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Science Immunology Pub Date : 2024-10-11 DOI: 10.1126/sciimmunol.adp5216

Daniel Malouli, Husam Taher, Mandana Mansouri, Ravi F. Iyer, Jason Reed, Courtney Papen, John B. Schell, Teresa Beechwood, Thomas Martinson, David Morrow, Colette M. Hughes, Roxanne M. Gilbride, Kurt Randall, Julia C. Ford, Karina Belica, Sohita Ojha, Jonah B. Sacha, Benjamin N. Bimber, Scott G. Hansen, Louis J. Picker, Klaus Früh

{"title":"Human cytomegalovirus UL18 prevents priming of MHC-E– and MHC-II–restricted CD8+ T cells","authors":"Daniel Malouli, Husam Taher, Mandana Mansouri, Ravi F. Iyer, Jason Reed, Courtney Papen, John B. Schell, Teresa Beechwood, Thomas Martinson, David Morrow, Colette M. Hughes, Roxanne M. Gilbride, Kurt Randall, Julia C. Ford, Karina Belica, Sohita Ojha, Jonah B. Sacha, Benjamin N. Bimber, Scott G. Hansen, Louis J. Picker, Klaus Früh","doi":"10.1126/sciimmunol.adp5216","DOIUrl":"10.1126/sciimmunol.adp5216","url":null,"abstract":"<div >Rhesus cytomegalovirus (RhCMV) vectors elicit major histocompatibility complex (MHC)–E–restricted CD8<sup>+</sup> T cells that stringently control simian immunodeficiency virus (SIV) in rhesus macaques. These responses require deletion of eight RhCMV chemokine-like open reading frames (ORFs) that are conserved in human cytomegalovirus (HCMV). To determine whether HCMV encodes additional, nonconserved inhibitors of unconventional T cell priming, we inserted 41 HCMV-specific ORFs into a chemokine-deficient strain (68-1 RhCMV). Monitoring of epitope recognition revealed that HCMV UL18 prevented unconventional T cell priming, resulting in MHC-Ia–targeted responses. UL18 is homologous to MHC-I but does not engage T cell receptors and, instead, binds with high affinity to inhibitory leukocyte immunoglobulin-like receptor–1 (LIR-1). UL18 lacking LIR-1 binding no longer interfered with MHC-E–restricted T cell stimulation by RhCMV-infected cells or the induction of unconventionally restricted T cells. Thus, LIR-1 binding needs to be deleted from UL18 of HCMV/HIV vaccines to allow for the induction of protective MHC-E–restricted T cells.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 100","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406788","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}

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Dendritic cells in a pinch: Migration during homeostasis 紧要关头的树突状细胞：平衡过程中的迁移

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Science Immunology Pub Date : 2024-10-04 DOI: 10.1126/sciimmunol.adt3806

Eli C. Olson, Stephanie C. Eisenbarth

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Oncogenic KRAS drives immunosuppression of colorectal cancer by impairing DDX60-mediated dsRNA accumulation and viral mimicry 致癌 KRAS 通过损害 DDX60 介导的 dsRNA 积累和病毒拟态，驱动结直肠癌的免疫抑制作用

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Science Immunology Pub Date : 2024-10-04 DOI: 10.1126/sciimmunol.ado8758

Yi Zhou, Yaxin Zhang, Mingzhou Li, Tian Ming, Chao Zhang, Chengmei Huang, Jiexi Li, Fengtian Li, Huali Li, Enen Zhao, Feng Shu, Lingtao Liu, Xingyan Pan, Yijun Gao, Lin Tian, Libing Song, Huilin Huang, Wenting Liao

{"title":"Oncogenic KRAS drives immunosuppression of colorectal cancer by impairing DDX60-mediated dsRNA accumulation and viral mimicry","authors":"Yi Zhou, Yaxin Zhang, Mingzhou Li, Tian Ming, Chao Zhang, Chengmei Huang, Jiexi Li, Fengtian Li, Huali Li, Enen Zhao, Feng Shu, Lingtao Liu, Xingyan Pan, Yijun Gao, Lin Tian, Libing Song, Huilin Huang, Wenting Liao","doi":"10.1126/sciimmunol.ado8758","DOIUrl":"10.1126/sciimmunol.ado8758","url":null,"abstract":"<div >The interferon (IFN) response is vital for the effectiveness of immune checkpoint inhibition (ICI) therapy. Our previous research showed that KRAS (Kirsten rat sarcoma viral) mutation impairs the IFN response in colorectal cancer (CRC), with an unclear mechanism. Here, we demonstrate that KRAS accelerates double-stranded RNA (dsRNA) degradation, impairing dsRNA sensing and IFN response by down-regulating DExD/H-box helicase 6 (DDX60). DDX60 was identified as a KRAS target here and could bind to dsRNAs to protect against RNA-induced silencing complex (RISC)–mediated degradation. Overexpressing DDX60 induced dsRNA accumulation, reactivated IFN signaling, and increased CRC sensitivity to ICI therapy. Mechanistically, KRAS engaged the AKT (also known as protein kinase B)–GSK3β (glycogen synthase kinase-3 beta) pathway to suppress STAT3 phosphorylation, thereby inhibiting STAT3-driven DDX60 transcription. Our findings reveal a role for KRAS in dsRNA homeostasis, suggesting potential strategies to convert “cold” tumors to “hot” and to overcome ICI resistance in CRC with KRAS mutations.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 100","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374627","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}

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