Pub Date : 2024-06-14DOI: 10.1126/sciimmunol.adp4474
Stephanie A. Ragland, Jonathan C. Kagan
Single-stranded DNA containing CGT/A motifs binds to the helicase domain of Schlafen 11 (SLFN11) to initiate cell death and cytokine production via SLFN11 ribonuclease activity (see related Research Article by Zhang et al.).
{"title":"Waking the sleeping giant: Single-stranded DNA binds Schlafen 11 to initiate innate immune responses","authors":"Stephanie A. Ragland, Jonathan C. Kagan","doi":"10.1126/sciimmunol.adp4474","DOIUrl":"10.1126/sciimmunol.adp4474","url":null,"abstract":"<div >Single-stranded DNA containing CGT/A motifs binds to the helicase domain of Schlafen 11 (SLFN11) to initiate cell death and cytokine production via SLFN11 ribonuclease activity (see related Research Article by Zhang <i>et al.</i>).</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 96","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321588","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}
Pub Date : 2024-06-14DOI: 10.1126/sciimmunol.add6774
Leon U. B. Enk, Malte Hellmig, Kristoffer Riecken, Christoph Kilian, Paul Datlinger, Saskia L. Jauch-Speer, Tobias Neben, Zeba Sultana, Varshi Sivayoganathan, Alina Borchers, Hans-Joachim Paust, Yu Zhao, Nariaki Asada, Shuya Liu, Theodora Agalioti, Penelope Pelczar, Thorsten Wiech, Christoph Bock, Tobias B. Huber, Samuel Huber, Stefan Bonn, Nicola Gagliani, Boris Fehse, Ulf Panzer, Christian F. Krebs
Pro-inflammatory CD4+ T cells are major drivers of autoimmune diseases, yet therapies modulating T cell phenotypes to promote an anti-inflammatory state are lacking. Here, we identify T helper 17 (TH17) cell plasticity in the kidneys of patients with antineutrophil cytoplasmic antibody–associated glomerulonephritis on the basis of single-cell (sc) T cell receptor analysis and scRNA velocity. To uncover molecules driving T cell polarization and plasticity, we established an in vivo pooled scCRISPR droplet sequencing (iCROP-seq) screen and applied it to mouse models of glomerulonephritis and colitis. CRISPR-based gene targeting in TH17 cells could be ranked according to the resulting transcriptional perturbations, and polarization biases into T helper 1 (TH1) and regulatory T cells could be quantified. Furthermore, we show that iCROP-seq can facilitate the identification of therapeutic targets by efficient functional stratification of genes and pathways in a disease- and tissue-specific manner. These findings uncover TH17 to TH1 cell plasticity in the human kidney in the context of renal autoimmunity.
促炎性 CD4+ T 细胞是自身免疫性疾病的主要驱动因素，但目前还缺乏调节 T 细胞表型以促进抗炎状态的疗法。在这里，我们根据单细胞（sc）T细胞受体分析和scRNA速度，确定了抗中性粒细胞胞浆抗体相关性肾小球肾炎患者肾脏中T辅助细胞17（TH17）的可塑性。为了发现驱动 T 细胞极化和可塑性的分子，我们建立了体内集合 scCRISPR 液滴测序（iCROP-seq）筛选，并将其应用于肾小球肾炎和结肠炎小鼠模型。基于CRISPR的TH17细胞基因打靶可根据所产生的转录扰动进行排序，并可量化T辅助细胞1（TH1）和调节性T细胞的极化偏向。此外，我们还发现，iCROP-seq 能以疾病和组织特异性的方式对基因和通路进行有效的功能分层，从而促进治疗靶点的确定。这些发现揭示了肾脏自身免疫背景下人类肾脏中 TH17 到 TH1 细胞的可塑性。
{"title":"Targeting T cell plasticity in kidney and gut inflammation by pooled single-cell CRISPR screening","authors":"Leon U. B. Enk, Malte Hellmig, Kristoffer Riecken, Christoph Kilian, Paul Datlinger, Saskia L. Jauch-Speer, Tobias Neben, Zeba Sultana, Varshi Sivayoganathan, Alina Borchers, Hans-Joachim Paust, Yu Zhao, Nariaki Asada, Shuya Liu, Theodora Agalioti, Penelope Pelczar, Thorsten Wiech, Christoph Bock, Tobias B. Huber, Samuel Huber, Stefan Bonn, Nicola Gagliani, Boris Fehse, Ulf Panzer, Christian F. Krebs","doi":"10.1126/sciimmunol.add6774","DOIUrl":"10.1126/sciimmunol.add6774","url":null,"abstract":"<div >Pro-inflammatory CD4<sup>+</sup> T cells are major drivers of autoimmune diseases, yet therapies modulating T cell phenotypes to promote an anti-inflammatory state are lacking. Here, we identify T helper 17 (T<sub>H</sub>17) cell plasticity in the kidneys of patients with antineutrophil cytoplasmic antibody–associated glomerulonephritis on the basis of single-cell (sc) T cell receptor analysis and scRNA velocity. To uncover molecules driving T cell polarization and plasticity, we established an in vivo pooled scCRISPR droplet sequencing (iCROP-seq) screen and applied it to mouse models of glomerulonephritis and colitis. CRISPR-based gene targeting in T<sub>H</sub>17 cells could be ranked according to the resulting transcriptional perturbations, and polarization biases into T helper 1 (T<sub>H</sub>1) and regulatory T cells could be quantified. Furthermore, we show that iCROP-seq can facilitate the identification of therapeutic targets by efficient functional stratification of genes and pathways in a disease- and tissue-specific manner. These findings uncover T<sub>H</sub>17 to T<sub>H</sub>1 cell plasticity in the human kidney in the context of renal autoimmunity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 96","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321587","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}
Pub Date : 2024-06-14DOI: 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
Expression of the long noncoding RNA (lncRNA) metastasis–associated lung adenocarcinoma transcript 1 (MALAT1) correlates with tumor progression and metastasis in many tumor types. However, the impact and mechanism of action by which MALAT1 promotes metastatic disease remain elusive. Here, we used CRISPR activation (CRISPRa) to overexpress MALAT1/Malat1 in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. Malat1 overexpression was sufficient to promote the progression of LUAD to metastatic disease in mice. Overexpression of MALAT1/Malat1 enhanced cell mobility and promoted the recruitment of protumorigenic macrophages to the tumor microenvironment through paracrine secretion of CCL2/Ccl2. Ccl2 up-regulation was the result of increased global chromatin accessibility upon Malat1 overexpression. Macrophage depletion and Ccl2 blockade counteracted the effects of Malat1 overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment.
{"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":"9 96","pages":""},"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}
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.
{"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":"9 96","pages":""},"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}
Pub Date : 2024-06-07DOI: 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
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.
在本体发育过程中，γδ T 细胞从胸腺中萌发并直接播种到外周组织中，以实现原位免疫。然而，γδT 细胞在人体中的功能作用主要是从血液中确定的。在这里，我们分析了 176 名捐献者的血液、粘膜和淋巴组织中人类γδ T 细胞在整个生命周期中的表型、转录组、功能和细胞群。在生命早期，克隆多样化的 Vδ1 亚群在血液和组织中占主导地位，包括幼稚和分化的效应细胞和组织修复功能，而细胞溶解性 Vδ2 亚群则遍布血液、脾脏和肺部。随着年龄的增长，Vδ1 和 Vδ2 亚群表现出克隆扩张和细胞溶解特征的增强，并在不同部位扩散。在成人中，Vδ2 细胞在血液中占主导地位，而 Vδ1 细胞则富集于各组织中，并表达驻留特征。因此，童年时期的抗原暴露推动了γδT细胞的功能进化和组织分区，导致其在免疫中发挥与年龄相关的作用。
{"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":"9 96","pages":""},"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}
Pub Date : 2024-06-07DOI: 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
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 Gβ4 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 Gβ4-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 Gβ4. In Gβ4 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.
嗜中性粒细胞和巨噬细胞等专业吞噬细胞严格控制着它们的吞噬对象、吞噬量以及货物摄取后的移动时间。我们的研究表明，质膜丰度是这些细胞行为的关键仲裁者。缺乏 G 蛋白亚基 Gβ4 的中性粒细胞和巨噬细胞表现出极度的质膜扩张，同时质膜张力明显下降。这些生物物理变化促进了对细菌、真菌、凋亡尸体和癌细胞的吞噬。我们还发现，Gβ4缺陷的中性粒细胞在摄取货物后不能正常抑制迁移。在缺乏 Gβ4 的细胞中，鞘脂合成通过驱动质膜积聚在这些表型中发挥了核心作用。在 Gβ4 基因敲除的小鼠中，中性粒细胞不仅对肺部吸入的真菌分生孢子的吞噬能力增强，而且吞噬的病原体向其他器官的迁移能力也增强了。这些结果共同揭示了一种意想不到的生物物理控制机制，它是骨髓功能决策的核心。
{"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":"9 96","pages":""},"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}
Pub Date : 2024-06-07DOI: 10.1126/sciimmunol.adq7287
Sindhura Siddapureddy, Stephanie Eisenbarth
Single-cell studies of human tissues reveal a stem-like TH2 subset as progenitors of key effectors in chronic type 2 inflammation.
对人体组织的单细胞研究显示，在慢性 2 型炎症中，干样 TH2 亚群是关键效应因子的祖先。
{"title":"The aMPPle differentiation potential of TH2 cells in human allergy","authors":"Sindhura Siddapureddy, Stephanie Eisenbarth","doi":"10.1126/sciimmunol.adq7287","DOIUrl":"10.1126/sciimmunol.adq7287","url":null,"abstract":"<div >Single-cell studies of human tissues reveal a stem-like T<sub>H</sub>2 subset as progenitors of key effectors in chronic type 2 inflammation.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 96","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288555","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}
Pub Date : 2024-06-07DOI: 10.1126/sciimmunol.adq7284
Annabel Wallace, Kevin C. O’Connor
Whole-proteome autoantibody profiling reveals an immunological signature that predates the clinical onset of multiple sclerosis.
全蛋白组自身抗体分析揭示了多发性硬化症临床发病前的免疫特征。
{"title":"Hide-&-Go-PhiP-Seq: Finding an elusive predictive MS biomarker","authors":"Annabel Wallace, Kevin C. O’Connor","doi":"10.1126/sciimmunol.adq7284","DOIUrl":"10.1126/sciimmunol.adq7284","url":null,"abstract":"<div >Whole-proteome autoantibody profiling reveals an immunological signature that predates the clinical onset of multiple sclerosis.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 96","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288551","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}
Pub Date : 2024-06-07DOI: 10.1126/sciimmunol.adk8141
Taylor A. Heim, Austin C. Schultz, Ines Delclaux, Vanessa Cristaldi, Madeline J. Churchill, Katherine S. Ventre, Amanda W. Lund
Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (TRMs) play an important role in site-specific immune memory, yet how LN TRMs form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8+ T cells as they seeded skin and LN TRMs using a model of vaccinia virus–induced skin infection. LN TRMs localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8+ T cells from the skin, already poised for residence. Effector CD8+ T cell transit through skin was required to populate LN TRMs in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN TRMs were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8+ T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.
淋巴运输塑造了淋巴结（LN）的同种免疫复合物。淋巴结驻留的记忆 T 细胞（TRMs）在特定部位的免疫记忆中发挥着重要作用，但淋巴结 TRMs 在病毒感染后如何重新形成仍不清楚。在这里，我们利用疫苗病毒诱导的皮肤感染模型追踪了抗病毒 CD8+ T 细胞在皮肤和 LN TRMs 上播种时的解剖分布。LN TRMs定位于受感染皮肤的引流LNs（dLNs），它们的形成依赖于效应CD8+ T细胞从皮肤的淋巴排出，而效应CD8+ T细胞已经做好了定居的准备。效应CD8+ T细胞穿过皮肤是在dLNs中形成LN TRMs的必要条件，皮肤中的抗原相遇强化了这一过程。此外，在没有循环记忆 T 细胞的情况下，LN TRMs 对病毒再侵具有保护作用。这些数据表明，在病毒清除过程中，组织浸润的 CD8+ T 细胞亚群从组织中排出，并在 dLN 盆地建立了一层区域保护。
{"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":"9 96","pages":""},"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}
Pub Date : 2024-05-31DOI: 10.1126/sciimmunol.adq3365
{"title":"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.","authors":"","doi":"10.1126/sciimmunol.adq3365","DOIUrl":"10.1126/sciimmunol.adq3365","url":null,"abstract":"","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 95","pages":""},"PeriodicalIF":17.6,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141966303","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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