Science Immunology最新文献_第8页

Overexpression of Malat1 drives metastasis through inflammatory reprogramming of the tumor microenvironment Malat1 的过表达通过肿瘤微环境的炎症重编程驱动转移。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-06-14 DOI: 10.1126/sciimmunol.adh5462

Elena Martinez-Terroba, Leah M. Plasek-Hegde, Ioannis Chiotakakos, Vincent Li, Fernando J. de Miguel, Camila Robles-Oteiza, Antariksh Tyagi, Katerina Politi, Jesse R. Zamudio, Nadya Dimitrova

{"title":"Overexpression of Malat1 drives metastasis through inflammatory reprogramming of the tumor microenvironment","authors":"Elena Martinez-Terroba, Leah M. Plasek-Hegde, Ioannis Chiotakakos, Vincent Li, Fernando J. de Miguel, Camila Robles-Oteiza, Antariksh Tyagi, Katerina Politi, Jesse R. Zamudio, Nadya Dimitrova","doi":"10.1126/sciimmunol.adh5462","DOIUrl":"10.1126/sciimmunol.adh5462","url":null,"abstract":"<div >Expression of the long noncoding RNA (lncRNA) metastasis–associated lung adenocarcinoma transcript 1 (<i>MALAT1</i>) correlates with tumor progression and metastasis in many tumor types. However, the impact and mechanism of action by which <i>MALAT1</i> promotes metastatic disease remain elusive. Here, we used CRISPR activation (CRISPRa) to overexpress <i>MALAT1/Malat1</i> in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. <i>Malat1</i> overexpression was sufficient to promote the progression of LUAD to metastatic disease in mice. Overexpression of <i>MALAT1/Malat1</i> enhanced cell mobility and promoted the recruitment of protumorigenic macrophages to the tumor microenvironment through paracrine secretion of CCL2/Ccl2. <i>Ccl2</i> up-regulation was the result of increased global chromatin accessibility upon <i>Malat1</i> overexpression. Macrophage depletion and Ccl2 blockade counteracted the effects of <i>Malat1</i> overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321585","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

Schlafen 11 triggers innate immune responses through its ribonuclease activity upon detection of single-stranded DNA Schlafen 11 在检测到单链 DNA 时通过核糖核酸酶活性触发先天性免疫反应。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-06-14 DOI: 10.1126/sciimmunol.adj5465

Peng Zhang, Xiaoqing Hu, Zekun Li, Qian Liu, Lele Liu, Yingying Jin, Sizhe Liu, Xiang Zhao, Jianqiao Wang, Delong Hao, Houzao Chen, Depei Liu

{"title":"Schlafen 11 triggers innate immune responses through its ribonuclease activity upon detection of single-stranded DNA","authors":"Peng Zhang, Xiaoqing Hu, Zekun Li, Qian Liu, Lele Liu, Yingying Jin, Sizhe Liu, Xiang Zhao, Jianqiao Wang, Delong Hao, Houzao Chen, Depei Liu","doi":"10.1126/sciimmunol.adj5465","DOIUrl":"10.1126/sciimmunol.adj5465","url":null,"abstract":"<div >Nucleic acids are major structures detected by the innate immune system. Although intracellular single-stranded DNA (ssDNA) accumulates during pathogen infection or disease, it remains unclear whether and how intracellular ssDNA stimulates the innate immune system. Here, we report that intracellular ssDNA triggers cytokine expression and cell death in a CGT motif–dependent manner. We identified Schlafen 11 (SLFN11) as an ssDNA-activated RNase, which is essential for the innate immune responses induced by intracellular ssDNA and adeno-associated virus infection. We found that SLFN11 directly binds ssDNA containing CGT motifs through its carboxyl-terminal domain, translocates to the cytoplasm upon ssDNA recognition, and triggers innate immune responses through its amino-terminal ribonuclease activity that cleaves transfer RNA (tRNA). Mice deficient in Slfn9, a mouse homolog of SLFN11, exhibited resistance to CGT ssDNA–induced inflammation, acute hepatitis, and septic shock. This study identifies CGT ssDNA and SLFN11/9 as a class of immunostimulatory nucleic acids and pattern recognition receptors, respectively, and conceptually couples DNA immune sensing to controlled RNase activation and tRNA cleavage.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321586","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

Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span 不同组织中的人γδ T 细胞在整个生命周期中表现出特定部位的成熟动态。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-06-07 DOI: 10.1126/sciimmunol.adn3954

Joshua I. Gray, Daniel P. Caron, Steven B. Wells, Rebecca Guyer, Peter Szabo, Daniel Rainbow, Can Ergen, Ksenia Rybkina, Marissa C. Bradley, Rei Matsumoto, Kalpana Pethe, Masaru Kubota, Sarah Teichmann, Joanne Jones, Nir Yosef, Mark Atkinson, Maigan Brusko, Todd M. Brusko, Thomas J. Connors, Peter A. Sims, Donna L. Farber

{"title":"Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span","authors":"Joshua I. Gray, Daniel P. Caron, Steven B. Wells, Rebecca Guyer, Peter Szabo, Daniel Rainbow, Can Ergen, Ksenia Rybkina, Marissa C. Bradley, Rei Matsumoto, Kalpana Pethe, Masaru Kubota, Sarah Teichmann, Joanne Jones, Nir Yosef, Mark Atkinson, Maigan Brusko, Todd M. Brusko, Thomas J. Connors, Peter A. Sims, Donna L. Farber","doi":"10.1126/sciimmunol.adn3954","DOIUrl":"10.1126/sciimmunol.adn3954","url":null,"abstract":"<div >During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity. However, their functional role in humans has largely been defined from blood. Here, we analyzed the phenotype, transcriptome, function, and repertoire of human γδ T cells in blood and mucosal and lymphoid tissues from 176 donors across the life span, revealing distinct profiles in children compared with adults. In early life, clonally diverse Vδ1 subsets predominate across blood and tissues, comprising naïve and differentiated effector and tissue repair functions, whereas cytolytic Vδ2 subsets populate blood, spleen, and lungs. With age, Vδ1 and Vδ2 subsets exhibit clonal expansions and elevated cytolytic signatures, which are disseminated across sites. In adults, Vδ2 cells predominate in blood, whereas Vδ1 cells are enriched across tissues and express residency profiles. Thus, antigenic exposures over childhood drive the functional evolution and tissue compartmentalization of γδ T cells, leading to age-dependent roles in immunity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adn3954","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288552","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

Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells 质膜丰度决定髓系细胞的吞噬能力和功能性交叉对话。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-06-07 DOI: 10.1126/sciimmunol.adl2388

Benjamin Y. Winer, Alexander H. Settle, Alexandrina M. Yakimov, Carlos Jeronimo, Tomi Lazarov, Murray Tipping, Michelle Saoi, Anjelique Sawh, Anna-Liisa L. Sepp, Michael Galiano, Justin S. A. Perry, Yung Yu Wong, Frederic Geissmann, Justin Cross, Ting Zhou, Lance C. Kam, H. Amalia Pasolli, Tobias Hohl, Jason G. Cyster, Orion D. Weiner, Morgan Huse

{"title":"Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells","authors":"Benjamin Y. Winer, Alexander H. Settle, Alexandrina M. Yakimov, Carlos Jeronimo, Tomi Lazarov, Murray Tipping, Michelle Saoi, Anjelique Sawh, Anna-Liisa L. Sepp, Michael Galiano, Justin S. A. Perry, Yung Yu Wong, Frederic Geissmann, Justin Cross, Ting Zhou, Lance C. Kam, H. Amalia Pasolli, Tobias Hohl, Jason G. Cyster, Orion D. Weiner, Morgan Huse","doi":"10.1126/sciimmunol.adl2388","DOIUrl":"10.1126/sciimmunol.adl2388","url":null,"abstract":"<div >Professional phagocytes like neutrophils and macrophages tightly control what they consume, how much they consume, and when they move after cargo uptake. We show that plasma membrane abundance is a key arbiter of these cellular behaviors. Neutrophils and macrophages lacking the G protein subunit Gβ<sub>4</sub> exhibited profound plasma membrane expansion, accompanied by marked reduction in plasma membrane tension. These biophysical changes promoted the phagocytosis of bacteria, fungus, apoptotic corpses, and cancer cells. We also found that Gβ<sub>4</sub>-deficient neutrophils are defective in the normal inhibition of migration following cargo uptake. Sphingolipid synthesis played a central role in these phenotypes by driving plasma membrane accumulation in cells lacking Gβ<sub>4</sub>. In Gβ<sub>4</sub> knockout mice, neutrophils not only exhibited enhanced phagocytosis of inhaled fungal conidia in the lung but also increased trafficking of engulfed pathogens to other organs. Together, these results reveal an unexpected, biophysical control mechanism central to myeloid functional decision-making.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288554","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

The aMPPle differentiation potential of TH2 cells in human allergy 人类过敏症中 TH2 细胞的分化潜能。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-06-07 DOI: 10.1126/sciimmunol.adq7287

Sindhura Siddapureddy, Stephanie Eisenbarth

引用次数: 0

Hide-&-Go-PhiP-Seq: Finding an elusive predictive MS biomarker Hide-&-Go-PhiP-Seq：寻找难以捉摸的预测性 MS 生物标记物。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-06-07 DOI: 10.1126/sciimmunol.adq7284

Annabel Wallace, Kevin C. O’Connor

引用次数: 0

Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes 淋巴管转运为皮肤引流淋巴结中的细胞毒性常驻记忆 T 细胞播下了种子。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-06-07 DOI: 10.1126/sciimmunol.adk8141

Taylor A. Heim, Austin C. Schultz, Ines Delclaux, Vanessa Cristaldi, Madeline J. Churchill, Katherine S. Ventre, Amanda W. Lund

{"title":"Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes","authors":"Taylor A. Heim, Austin C. Schultz, Ines Delclaux, Vanessa Cristaldi, Madeline J. Churchill, Katherine S. Ventre, Amanda W. Lund","doi":"10.1126/sciimmunol.adk8141","DOIUrl":"10.1126/sciimmunol.adk8141","url":null,"abstract":"<div >Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (T<sub>RMs</sub>) play an important role in site-specific immune memory, yet how LN T<sub>RMs</sub> form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8<sup>+</sup> T cells as they seeded skin and LN T<sub>RMs</sub> using a model of vaccinia virus–induced skin infection. LN T<sub>RMs</sub> localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8<sup>+</sup> T cells from the skin, already poised for residence. Effector CD8<sup>+</sup> T cell transit through skin was required to populate LN T<sub>RMs</sub> in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN T<sub>RMs</sub> were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8<sup>+</sup> T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288553","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 “TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf” by Y. Chang et al. Y. Chang 等人的研究文章 "TGF-β 通过 c-Maf 指定小鼠 CD4+ T 细胞中 TFH 与 TH17 细胞的命运 "的勘误。

IF 17.6 1区医学

Science Immunology Pub Date : 2024-05-31 DOI: 10.1126/sciimmunol.adq3365

引用次数: 0

Erratum for the Research Article “TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf” by Y. Chang et al. Y. Chang 等人的研究文章 "TGF-β 通过 c-Maf 指定小鼠 CD4+ T 细胞中 TFH 与 TH17 细胞的命运 "的勘误。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-31 DOI: 10.1126/sciimmunol.adq3385

引用次数: 0

GFI1B specifies developmental potential of innate lymphoid cell progenitors in the lungs GFI1B 可指定肺部先天性淋巴细胞祖细胞的发育潜能。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-31 DOI: 10.1126/sciimmunol.adj2654

Qiutong Huang, Wang H. J. Cao, Sophie Curio, Huiyang Yu, Renae Denman, Evelyn Chen, Jaring Schreuder, James Dight, M. Zeeshan Chaudhry, Nicolas Jacquelot, Verena C. Wimmer, Cyril Seillet, Tarik Möröy, Gabrielle T. Belz

{"title":"GFI1B specifies developmental potential of innate lymphoid cell progenitors in the lungs","authors":"Qiutong Huang, Wang H. J. Cao, Sophie Curio, Huiyang Yu, Renae Denman, Evelyn Chen, Jaring Schreuder, James Dight, M. Zeeshan Chaudhry, Nicolas Jacquelot, Verena C. Wimmer, Cyril Seillet, Tarik Möröy, Gabrielle T. Belz","doi":"10.1126/sciimmunol.adj2654","DOIUrl":"10.1126/sciimmunol.adj2654","url":null,"abstract":"<div >Tissue-resident innate lymphoid cells (ILCs) play a vital role in the frontline defense of various tissues, including the lung. The development of type 2 ILCs (ILC2s) depends on transcription factors such as GATA3, RORα, GFI1, and Bcl11b; however, the factors regulating lung-resident ILC2s remain unclear. Through fate mapping analysis of the paralog transcription factors GFI1 and GFI1B, we show that GFI1 is consistently expressed during the transition from progenitor to mature ILC2s. In contrast, GFI1B expression is limited to specific subsets of bone marrow progenitors and lung-resident ILC progenitors. We found that GFI1B<sup>+</sup> lung ILC progenitors represent a multi-lineage subset with tissue-resident characteristics and the potential to form lung-derived ILC subsets and liver-resident ILC1s. Loss of GFI1B in bone marrow progenitors led to the selective loss of lung-resident IL-18R<sup>+</sup> ILCs and mature ILC2, subsequently preventing the emergence of effector ILCs that could protect the lung against inflammatory or tumor challenge.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":null,"pages":null},"PeriodicalIF":24.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184449","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