Science Immunology最新文献_第10页

Erratum for the Research Article “Transcriptomes and metabolism define mouse and human MAIT cell populations” by S. Chandra et al. S. Chandra 等人的研究文章 "转录组和新陈代谢界定了小鼠和人类 MAIT 细胞群 "的勘误。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-10 DOI: 10.1126/sciimmunol.adp9609

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Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity 对中枢神经系统自身免疫患者进行抗 BCMA CAR T 细胞疗法的单细胞分析。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-10 DOI: 10.1126/sciimmunol.adj9730

Chuan Qin, Min Zhang, Da-Peng Mou, Luo-Qi Zhou, Ming-Hao Dong, Liang Huang, Wen Wang, Song-Bai Cai, Yun-Fan You, Ke Shang, Jun Xiao, Di Wang, Chun-Rui Li, Yi Hao, Michael Heming, Long-Jun Wu, Gerd Meyer Zu Hörste, Chen Dong, Bi-Tao Bu, Dai-Shi Tian, Wei Wang

{"title":"Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity","authors":"Chuan Qin, Min Zhang, Da-Peng Mou, Luo-Qi Zhou, Ming-Hao Dong, Liang Huang, Wen Wang, Song-Bai Cai, Yun-Fan You, Ke Shang, Jun Xiao, Di Wang, Chun-Rui Li, Yi Hao, Michael Heming, Long-Jun Wu, Gerd Meyer Zu Hörste, Chen Dong, Bi-Tao Bu, Dai-Shi Tian, Wei Wang","doi":"10.1126/sciimmunol.adj9730","DOIUrl":"10.1126/sciimmunol.adj9730","url":null,"abstract":"<div >Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti–B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8<sup>+</sup> CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 95","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adj9730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905013","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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A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression 乳酸-SREBP2 信号轴驱动耐受性树突状细胞成熟并促进癌症进展。

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-10 DOI: 10.1126/sciimmunol.adi4191

Michael P. Plebanek, Yue Xue, Y-Van Nguyen, Nicholas C. DeVito, Xueying Wang, Alisha Holtzhausen, Georgia M. Beasley, Balamayooran Theivanthiran, Brent A. Hanks

{"title":"A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression","authors":"Michael P. Plebanek, Yue Xue, Y-Van Nguyen, Nicholas C. DeVito, Xueying Wang, Alisha Holtzhausen, Georgia M. Beasley, Balamayooran Theivanthiran, Brent A. Hanks","doi":"10.1126/sciimmunol.adi4191","DOIUrl":"10.1126/sciimmunol.adi4191","url":null,"abstract":"<div >Conventional dendritic cells (DCs) are essential mediators of antitumor immunity. As a result, cancers have developed poorly understood mechanisms to render DCs dysfunctional within the tumor microenvironment (TME). After identification of CD63 as a specific surface marker, we demonstrate that mature regulatory DCs (mregDCs) migrate to tumor-draining lymph node tissues and suppress DC antigen cross-presentation in trans while promoting T helper 2 and regulatory T cell differentiation. Transcriptional and metabolic studies showed that mregDC functionality is dependent on the mevalonate biosynthetic pathway and its master transcription factor, SREBP2. We found that melanoma-derived lactate activates SREBP2 in tumor DCs and drives conventional DC transformation into mregDCs via homeostatic or tolerogenic maturation. DC-specific genetic silencing and pharmacologic inhibition of SREBP2 promoted antitumor CD8<sup>+</sup> T cell activation and suppressed melanoma progression. CD63<sup>+</sup> mregDCs were found to reside within the lymph nodes of several preclinical tumor models and in the sentinel lymph nodes of patients with melanoma. Collectively, this work suggests that a tumor lactate-stimulated SREBP2-dependent program promotes CD63<sup>+</sup> mregDC development and function while serving as a promising therapeutic target for overcoming immune tolerance in the TME.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 95","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905055","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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Everlasting first impressions in B cells B 细胞中永恒的第一印象

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-03 DOI: 10.1126/sciimmunol.adq0015

Soyeon Kim, Jonathan S. Maltzman

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The immunoglobulin superfamily ligand B7H6 subjects T cell responses to NK cell surveillance 免疫球蛋白超家族配体 B7H6 使 T 细胞反应受 NK 细胞监控

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-03 DOI: 10.1126/sciimmunol.adj7970

Michael Kilian, Mirco J. Friedrich, Kevin Hai-Ning Lu, David Vonhören, Selina Jansky, Julius Michel, Anna Keib, Saskia Stange, Nicolaj Hackert, Niklas Kehl, Markus Hahn, Antje Habel, Stefanie Jung, Kristine Jähne, Felix Sahm, Johannes Betge, Adelheid Cerwenka, Frank Westermann, Peter Dreger, Marc S. Raab, Nadja M. Meindl-Beinker, Matthias Ebert, Lukas Bunse, Carsten Müller-Tidow, Michael Schmitt, Michael Platten

{"title":"The immunoglobulin superfamily ligand B7H6 subjects T cell responses to NK cell surveillance","authors":"Michael Kilian, Mirco J. Friedrich, Kevin Hai-Ning Lu, David Vonhören, Selina Jansky, Julius Michel, Anna Keib, Saskia Stange, Nicolaj Hackert, Niklas Kehl, Markus Hahn, Antje Habel, Stefanie Jung, Kristine Jähne, Felix Sahm, Johannes Betge, Adelheid Cerwenka, Frank Westermann, Peter Dreger, Marc S. Raab, Nadja M. Meindl-Beinker, Matthias Ebert, Lukas Bunse, Carsten Müller-Tidow, Michael Schmitt, Michael Platten","doi":"10.1126/sciimmunol.adj7970","DOIUrl":"10.1126/sciimmunol.adj7970","url":null,"abstract":"<div >Understanding the mechanisms that regulate T cell immunity is critical for the development of effective therapies for diseases associated with T cell dysfunction, including autoimmune diseases, chronic infections, and cancer. Co-inhibitory “checkpoint molecules,” such as programmed cell death protein-1, balance excessive or prolonged immune activation by T cell–intrinsic signaling. Here, by screening for mediators of natural killer (NK) cell recognition on T cells, we identified the immunoglobulin superfamily ligand B7H6 to be highly expressed by activated T cells, including patient-infused CD19-targeting chimeric antigen receptor (CAR) T cells. Unlike other checkpoint molecules, B7H6 mediated NKp30-dependent recognition and subsequent cytolysis of activated T cells by NK cells. B7H6<sup>+</sup> T cells were prevalent in the tissue and blood of several diseases, and their abundance in tumor tissue positively correlated with clinical response in a cohort of patients with immune checkpoint inhibitor–treated esophageal cancer. In humanized mouse models, NK cell surveillance via B7H6 limited the persistence and antitumor activity of CAR T cells, and its genetic deletion enhanced T cell proliferation and persistence. Together, we provide evidence of B7H6 protein expression by activated T cells and suggest the B7H6-NKp30 axis as a therapeutically actionable NK cell–dependent immune checkpoint that regulates human T cell function.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 95","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821582","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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A TH17-intrinsic IL-1β–STAT5 axis drives steroid resistance in autoimmune neuroinflammation TH17内在IL-1β-STAT5轴驱动自身免疫性神经炎症中的类固醇抗药性

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-03 DOI: 10.1126/sciimmunol.abq1558

William A. Miller-Little, Xing Chen, Vanessa Salazar, Caini Liu, Katarzyna Bulek, Julie Y. Zhou, Xiao Li, Olaf Stüve, Thaddeus Stappenbeck, George Dubyak, Junjie Zhao, Xiaoxia Li

{"title":"A TH17-intrinsic IL-1β–STAT5 axis drives steroid resistance in autoimmune neuroinflammation","authors":"William A. Miller-Little, Xing Chen, Vanessa Salazar, Caini Liu, Katarzyna Bulek, Julie Y. Zhou, Xiao Li, Olaf Stüve, Thaddeus Stappenbeck, George Dubyak, Junjie Zhao, Xiaoxia Li","doi":"10.1126/sciimmunol.abq1558","DOIUrl":"10.1126/sciimmunol.abq1558","url":null,"abstract":"<div >Steroid resistance poses a major challenge for the management of autoimmune neuroinflammation. T helper 17 (T<sub>H</sub>17) cells are widely implicated in the pathology of steroid resistance; however, the underlying mechanisms are unknown. In this study, we identified that interleukin-1 receptor (IL-1R) blockade rendered experimental autoimmune encephalomyelitis (EAE) mice sensitive to dexamethasone (Dex) treatment. Interleukin-1β (IL-1β) induced a signal transducer and activator of transcription 5 (STAT5)–mediated steroid-resistant transcriptional program in T<sub>H</sub>17 cells, which promoted inflammatory cytokine production and suppressed Dex-induced anti-inflammatory genes. T<sub>H</sub>17-specific deletion of STAT5 ablated the IL-1β–induced steroid-resistant transcriptional program and rendered EAE mice sensitive to Dex treatment. IL-1β synergized with Dex to promote the STAT5-dependent expression of CD69 and the development of central nervous system (CNS)–resident CD69<sup>+</sup> T<sub>H</sub>17 cells. Combined IL-1R blockade and Dex treatment ablated CNS-resident T<sub>H</sub>17 cells, reduced EAE severity, and prevented relapse. CD69<sup>+</sup> tissue-resident T<sub>H</sub>17 cells were also detected in brain lesions of patients with multiple sclerosis. These findings (i) demonstrate that IL-1β–STAT5 signaling in T<sub>H</sub>17 cells mediates steroid resistance and (ii) identify a therapeutic strategy for reversing steroid resistance in T<sub>H</sub>17-mediated CNS autoimmunity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 95","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821689","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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The Benjamin Button effect on stem cells: Reversing the clock on aging immunity 干细胞的本杰明-巴顿效应逆转衰老免疫的时钟

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-03 DOI: 10.1126/sciimmunol.adq0013

Luciana Conde, Carolina Lucas

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Oxidative phosphorylation regulates B cell effector cytokines and promotes inflammation in multiple sclerosis 氧化磷酸化调节 B 细胞效应细胞因子并促进多发性硬化症的炎症反应

IF 24.8 1区医学

Science Immunology Pub Date : 2024-05-03 DOI: 10.1126/sciimmunol.adk0865

Rui Li, Yanting Lei, Ayman Rezk, Diego A. Espinoza, Jing Wang, Huiru Feng, Bo Zhang, Isabella P. Barcelos, Hang Zhang, Jing Yu, Xinrui Huo, Fangyi Zhu, Changxin Yang, Hao Tang, Amy C. Goldstein, Brenda L. Banwell, Hakon Hakonarson, Hongwei Xu, Michael Mingueneau, Bo Sun, Hulun Li, Amit Bar-Or

{"title":"Oxidative phosphorylation regulates B cell effector cytokines and promotes inflammation in multiple sclerosis","authors":"Rui Li, Yanting Lei, Ayman Rezk, Diego A. Espinoza, Jing Wang, Huiru Feng, Bo Zhang, Isabella P. Barcelos, Hang Zhang, Jing Yu, Xinrui Huo, Fangyi Zhu, Changxin Yang, Hao Tang, Amy C. Goldstein, Brenda L. Banwell, Hakon Hakonarson, Hongwei Xu, Michael Mingueneau, Bo Sun, Hulun Li, Amit Bar-Or","doi":"10.1126/sciimmunol.adk0865","DOIUrl":"10.1126/sciimmunol.adk0865","url":null,"abstract":"<div >Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF–expressing) and anti-inflammatory (IL-10–expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)–induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a “fourth signal” that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 95","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821701","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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Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity 癌症中上调的 PLA2G10 会影响 T 细胞浸润，从而抑制免疫力

IF 24.8 1区医学

Science Immunology Pub Date : 2024-04-26 DOI: 10.1126/sciimmunol.adh2334

Tianxiang Zhang, Weiwei Yu, Xiaoxiao Cheng, Jacky Yeung, Viviana Ahumada, Paul C. Norris, Mackenzie J. Pearson, Xuan Yang, Willemijn van Deursen, Christina Halcovich, Ala Nassar, Mathew D. Vesely, Yu Zhang, Jianping Zhang, Lan Ji, Dallas B. Flies, Linda Liu, Solomon Langermann, William J. LaRochelle, Rachel Humphrey, Dejian Zhao, Qiuyu Zhang, Jindong Zhang, Runxia Gu, Kurt A. Schalper, Miguel F. Sanmamed, Lieping Chen

{"title":"Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity","authors":"Tianxiang Zhang, Weiwei Yu, Xiaoxiao Cheng, Jacky Yeung, Viviana Ahumada, Paul C. Norris, Mackenzie J. Pearson, Xuan Yang, Willemijn van Deursen, Christina Halcovich, Ala Nassar, Mathew D. Vesely, Yu Zhang, Jianping Zhang, Lan Ji, Dallas B. Flies, Linda Liu, Solomon Langermann, William J. LaRochelle, Rachel Humphrey, Dejian Zhao, Qiuyu Zhang, Jindong Zhang, Runxia Gu, Kurt A. Schalper, Miguel F. Sanmamed, Lieping Chen","doi":"10.1126/sciimmunol.adh2334","DOIUrl":"10.1126/sciimmunol.adh2334","url":null,"abstract":"<div >T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell–recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti–PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10’s enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 94","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651270","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

Targeted depletion of PD-1–expressing cells induces immune tolerance through peripheral clonal deletion 定向清除 PD-1 表达细胞，通过外周克隆删除诱导免疫耐受

IF 24.8 1区医学

Science Immunology Pub Date : 2024-04-26 DOI: 10.1126/sciimmunol.adh0085

Jikai Cui, Heng Xu, Jizhang Yu, Shuan Ran, Xi Zhang, Yuan Li, Zhang Chen, Yuqing Niu, Song Wang, Weicong Ye, Wenhao Chen, Jie Wu, Jiahong Xia

{"title":"Targeted depletion of PD-1–expressing cells induces immune tolerance through peripheral clonal deletion","authors":"Jikai Cui, Heng Xu, Jizhang Yu, Shuan Ran, Xi Zhang, Yuan Li, Zhang Chen, Yuqing Niu, Song Wang, Weicong Ye, Wenhao Chen, Jie Wu, Jiahong Xia","doi":"10.1126/sciimmunol.adh0085","DOIUrl":"10.1126/sciimmunol.adh0085","url":null,"abstract":"<div >Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)–mediated ablation of PD-1<sup>+</sup> cells reshaped the TCR repertoire through peripheral clonal deletion of alloreactive T cells and promoted tolerance in mouse transplantation models. In addition, by using PD-1–specific depleting antibodies, we found that antibody-mediated depletion of PD-1<sup>+</sup> cells prevented heart transplant rejection and the development of experimental autoimmune encephalomyelitis (EAE) in humanized PD-1 mice. Thus, these data suggest that PD-1 is an attractive target for peripheral clonal deletion and induction of immune tolerance.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 94","pages":""},"PeriodicalIF":24.8,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651275","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