International Reviews of Immunology最新文献

{"title":"Extracellular vesicles and mononuclear phagocyte axis: Interactions shaping immune responses.","authors":"Tulio J Lopera, Gloria Vásquez, Mauricio Rojas, Diana Castaño","doi":"10.1080/08830185.2025.2563523","DOIUrl":"https://doi.org/10.1080/08830185.2025.2563523","url":null,"abstract":"<p><p>Extracellular vesicles (EVs), nano-sized particles enclosed by a lipid membrane, play a pivotal role in cell-to-cell communication as essential mediators in various biological processes and diseases. Despite their ability to interact with multiple targets, EVs notably demonstrate a high affinity for specialized cells within the extracellular environment, particularly mononuclear phagocytes. The interaction between EVs and mononuclear phagocytes significantly affects the profile of these cells. Several factors, including vesicle cargo, size, parental cell origin, involved receptors, and the specific endocytic pathway, influence EVs' consequences and subsequent responses. Key components of mononuclear phagocytes, monocytes and macrophages, play a crucial role in the innate immune system, contributing to tissue damage, repair, remodeling, inflammation, homeostasis maintenance, and disease progression. Despite extensive research on EVs in various health and disease contexts, their precise impact on mononuclear phagocytes remains incompletely understood. Therefore, this review explores EVs' role in modulating monocyte and macrophage profiles and functions across different scenarios. It emphasizes that EVs actively shape the phenotype of these mononuclear phagocytes to maintain homeostasis and regulatory functions, but also induce pro-inflammatory polarization in infectious diseases, systemic inflammation, and autoimmunity. Simultaneously, during neoplastic or tumor development, the EV-mononuclear phagocyte axis prompts imbalanced responses, combining pro- and anti-inflammatory outcomes. These findings confirm EVs as promising tools for therapeutic strategies to modulate mononuclear phagocyte functions in diverse pathological settings.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-21"},"PeriodicalIF":2.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revolutionizing IBD therapy: Insights into contemporary treatment strategies.","authors":"Pooja Kushwaha, Rahila Qureshi, Nooruddin Khan, Sangita Mukhopadhyay","doi":"10.1080/08830185.2025.2563522","DOIUrl":"https://doi.org/10.1080/08830185.2025.2563522","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) varies in prevalence globally. Recent rise in IBD cases mirrors evolving health landscape due to urbanization and lifestyle changes worldwide. Existing drugs for IBD include aminosalicylates, corticosteroids, Immunomodulators, biologics, JAK inhibitors, and antibiotics. Although these medications are effective in managing symptoms and remission, these present several with limitations. Side effects such as nausea, infections, and liver toxicity are common, and some patients may develop resistance or lose response over time. Additionally, biologics can be costly, and immunosuppressive drugs raise concerns about long-term safety along increased risk of infection. Importantly, approximately 10% to 30% of the IBD patients do not respond to conventional treatments such as corticosteroids, immunosuppressants, or biologic therapies. Research continues to explore new treatments to address these limitations and improve outcomes for individuals with IBD. This review is an attempt to critically evaluate the currently available treatments for IBD underlining their limitations, and the pressing demand for innovative strategies. Further, we delve into the rationale behind peptide-based therapies, emphasizing their potential to modulate inflammation and promote mucosal healing. The work also highlights promising outcomes from recent preclinical and clinical studies underscoring the pivotal role of peptides in IBD management.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-25"},"PeriodicalIF":2.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-mediated membranous nephropathy: Innovations in pathogenetic modeling and mechanistic insights.","authors":"Chunjie Zhang, Zaiping Xu, Ye Feng, Jinrong Kong, Yunlai Wang, Fan Xu, Mo Yang","doi":"10.1080/08830185.2025.2550714","DOIUrl":"https://doi.org/10.1080/08830185.2025.2550714","url":null,"abstract":"<p><p>Membranous nephropathy (MN), an autoimmune cause of adult nephrotic syndrome, is driven by podocyte-targeting antibodies against PLA2R/THSD7A. Current models fail to fully capture human disease progression. This review evaluates three transformative approaches: (1) Heterologous antibody-induced models enabling acute injury replication; (2) Antigen-driven immunization modeling adaptive immunity; and (3) GBF-on-Chip platforms mimicking filtration barrier dynamics. Collectively, they reveal complement-dependent and direct podocytotoxic injury mechanisms. While antibody-induced models offer rapid injury induction and high reproducibility, their transient phenotype cannot model chronic progression or immune tolerance breakdown. Antigen-driven models recapitulate adaptive immunity but face prolonged timelines and epitope targeting bias diverging from human IgG4 dominance. GFB-on-Chip systems excel in mechanistic dissection of podocyte injury but lack immune microenvironment integration and physiologically accurate glomerular architecture. This review synthesizes strategies for MN model development through antibody-podocyte interaction studies, critically evaluates the strengths of existing platforms, and discusses emerging technologies for probing disease mechanisms and accelerating therapeutic discovery.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-drug conjugates in breast cancer: From therapeutic and immune activation mechanisms to resistance prevention.","authors":"Nik Mohd Asri Nik Amirah Auni, Norhanani Mohd Redzwan, Maya Mazuwin Yahya, Kah Keng Wong","doi":"10.1080/08830185.2025.2545364","DOIUrl":"10.1080/08830185.2025.2545364","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are produced by integrating the specificity of monoclonal antibodies with cytotoxic payloads. ADCs are vital biologics for breast cancer treatment where they not only exert direct cytotoxicity but also promote anti-tumor immune responses against breast cancers. In this review, the structure, mechanism of action, and the anti-tumor immune response properties of approved and emerging ADCs are presented and discussed. The FDA-approved ADCs include trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG-Trop2), and trastuzumab deruxtecan (T-DXd), as well as two emerging ADCs, i.e. datopotamab deruxtecan (Dato-DXd) and ladiratuzumab vedotin (LV). Preclinical and clinical studies demonstrate their efficacy in multiple breast cancer subtypes (e.g. HER2⁺ and triple negative breast cancers). These ADCs exert anti-tumor activity through cytotoxic effects and immune responses primarily by recruiting and activating cytotoxic T cells. Moreover, combining ADCs with immune checkpoint inhibitors (ICIs) shows enhanced therapeutic outcomes. ADCs resistance is caused by heterogeneous target antigens expression, modified ADC processing including endocytosis and lysosomal trafficking, as well as upregulated drug-efflux pumps that decrease payload concentration intracellularly. Strategies to mitigate ADCs resistance include multi-target ADCs, and stability-enhancing linkers that also reduce off-target toxicities. ADCs continue to play key roles in breast cancer treatment, while next-generation ADCs may address current ADCs' limitations and resistance mechanisms.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-23"},"PeriodicalIF":2.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between <i>CTLA4</i> polymorphisms and susceptibility to granulomatosis with polyangiitis.","authors":"Amirhosein Mohamadi, Naeim Ehtesham, Huriyeh Hashemi, Narges Ansari, Mohammad Javad Zavar, Seyyed Hossein Mousavi, Neda Eskandari, Mahboobeh Zarei, Fatemeh Khodabandehloo","doi":"10.1080/08830185.2025.2543084","DOIUrl":"https://doi.org/10.1080/08830185.2025.2543084","url":null,"abstract":"<p><strong>Background: </strong>Granulomatosis with polyangiitis (GPA) is an autoimmune condition. This study evaluated the relationship between <i>CTLA4</i> gene polymorphisms, specifically rs231775, rs5742909, and rs3087243, and the risk of developing GPA.</p><p><strong>Materials and methods: </strong>A case-control study was conducted with 217 participants, 102 individuals diagnosed with GPA, and 115 control subjects. The high-resolution melting (HRM) technique was used to genotype these polymorphisms.</p><p><strong>Results: </strong>For the rs231775 polymorphism, the combined frequencies of AG and GG genotypes suggested an increased risk for GPA. Additionally, the GPA group had a higher frequency of the G allele. Also, patients with GG and AG genotypes displayed elevated levels of certain laboratory indices. Regarding rs5742909, the combined frequencies of TC and TT genotypes were linked to a lower risk of GPA. Moreover, a significant increase in the frequency of the T allele was noted in the control group. Those with the CC genotype exhibited a notably higher incidence of specific laboratory indices and some clinical manifestations. Our study found no significant association between the rs3087243 variant and the risk of developing GPA, nor with clinical or laboratory parameters.</p><p><strong>Conclusion: </strong>The G allele of the rs231775 is associated with a heightened risk of developing GPA. Conversely, the T allele of the rs5742909 SNP offers a protective effect against GPA; however, the presence of the C allele positively correlates with some laboratory parameters and symptoms. Furthermore, the rs3087243 polymorphism does not seem to be linked to an increased risk of GPA.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phagosomal escape and sabotage: The role of ESX-1 and PDIMs in <i>Mycobacterium tuberculosis</i> pathogenesis.","authors":"Mohd Shariq, Farhan Ahmed, Onaiza Ansari, Anam Mursaleen, Javaid Ahmad Sheikh","doi":"10.1080/08830185.2025.2531828","DOIUrl":"https://doi.org/10.1080/08830185.2025.2531828","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) employs diverse virulence factors to evade immune defenses and persist intracellularly. The ESAT-6 secretion system-1 (ESX-1) type VII secretion system (T7SS) releases EsxA, EspA, and EspB, inducing phagosomal rupture and cytosolic access while triggering host defenses, including galectin recruitment and stress granule formation. To counteract host responses, <i>M. tb</i> utilizes phthiocerol dimycocerosates (PDIMs) to inhibit autophagy and LC3-associated phagocytosis (LAP) by suppressing NADPH oxidase (NOX2) recruitment and reactive oxygen species (ROS) production. Additionally, CspA blocks LC3 lipidation, impairing LAP activation and phagosome maturation. EsxG and EsxH interfere with ESCRT-mediated phagosomal repair, further enhancing intracellular survival. Cytosolic <i>M. tb</i> is ubiquitinated by host E3 ligases, marking it for selective autophagy (xenophagy), yet <i>M. tb</i> evades degradation by manipulating autophagic flux. Simultaneously, <i>M. tb</i>-derived DNA activates the cyclic GMP-AMP synthase-stimulator of interferon response cGAMP interactor 1 (CGAS-STING1) axis, leading to type I interferon (IFN) signaling and inflammasome activation, which drive IL-1B and IL-18 secretion, necrosis, and pyroptosis, facilitating bacterial dissemination. Additionally, exosomes released during infection disseminate bacterial components, modulating immune responses systemically. This review uniquely integrates current findings on the coordinated actions of ESX-1 T7SS and PDIMs in mediating phagosomal rupture and immune evasion, offering a unified framework for understanding <i>M. tb</i>'s intracellular survival strategies. By bridging lipid- and protein-mediated virulence mechanisms and their impact on host autophagy, inflammasome activation, and phagosomal repair pathways, this work provides novel insights into therapeutic targets aimed at restoring host immune function.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-27"},"PeriodicalIF":4.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cells in liver regeneration: Current evidence and potential clinical targets.","authors":"Hollie F Moore, Saba Usmani, Saied Froghi, Hassan Rashidi, Alberto Quaglia, Barry Fuller, Brian R Davidson","doi":"10.1080/08830185.2025.2531820","DOIUrl":"10.1080/08830185.2025.2531820","url":null,"abstract":"<p><p>The livers' ability to regenerate after injury has attracted the investigation of possible therapeutic targets for liver disease. Cells of the immune system are considered fundamental for the initiation, propagation, and termination of liver regeneration as they produce essential signaling molecules, such as cytokines, chemokines, and growth factors. Previous evidence mainly focused on macrophage involvement in liver regeneration, namely Kupffer cells which secrete mitogenic cytokines. However, recent evidence has implicated other immune cell subsets in liver regeneration including platelets, the complement system, dendritic cells, granulocytes, and innate and adaptive lymphocytes. The concurrent function of different immune cell subsets highlights functional redundancies between immune cells and the temporospatial dynamics of liver regeneration. In this review, we discuss our understanding of the role of immune cells in liver regeneration, recent advances and cellular targets identified for clinical therapy over the past decade.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-40"},"PeriodicalIF":2.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cell antigens: A key to optimizing CAR-T cell therapy.","authors":"Purva Khodke, Dhananjay Hasurkar, Aakanksha Upadhyay, Aditi Shedge, Rhea Sippy, Bajarang Vasant Kumbhar","doi":"10.1080/08830185.2025.2515839","DOIUrl":"10.1080/08830185.2025.2515839","url":null,"abstract":"<p><p>B-cells are vital immune cells that differentiate into plasma cells to produce antibodies targeting specific antigens. They also act as Antigen Presenting Cells, displaying processed antigens on Major Histocompatibility Complex class-II molecules to activate helper T-cells. This process triggers immune response and memory development. B-cells have surface antigens crucial for their function, which are often overexpressed in B cell cancers, making them targets for therapies like Chimeric Antigen Receptor (CAR) T-cell therapy. However, the choice of antigen is crucial. Tumor associated antigens are common but can cause off-target effects, while tumor specific antigens are more specific but less common. Furthermore, the precise epitope on the antigen recognized by the CAR-T cells significantly influences activation, which can also depend on the epitope's distance from the B-cell membrane. To facilitate the identification of extracellular regions of tumor antigens for CAR interactions, this review models tumor antigen structures embedded in the lipid bilayer, analyzing their roles and functions. Specifically, the characterization of B-cell surface antigens, encompassing their structural features and their potential as targets for CAR-T therapy are discussed. Each antigen is meticulously examined to gain insights into their specific roles within B cell biology and their potential as therapeutic targets. In conclusion, this review highlights the importance of understanding B cell antigens for the development of effective CAR-T cell therapies. The insights into antigen structures and functions presented here can guide the selection of optimal targets and the design of CAR-T cells to combat B cell malignancies effectively.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-28"},"PeriodicalIF":4.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunological insights into role of Th9 and Treg cell homeostasis and cytokines dynamics in the progression of diabetic nephropathy.","authors":"Manoj Khokhar, Purvi Purohit, Ashita Gadwal, Nitin Kumar Bajpai, Ravindra Kumar Shukla","doi":"10.1080/08830185.2025.2515836","DOIUrl":"https://doi.org/10.1080/08830185.2025.2515836","url":null,"abstract":"<p><strong>Background: </strong>T cells play a crucial role in immune responses and are involved in chronic diseases such as Type 2 Diabetes Mellitus (T2DM) and its complications, including Diabetic Nephropathy (DN). Among these, regulatory T cells (Treg) act as key regulators, while T helper 9 (Th9) cells, which produce IL-9, are essential in maintaining immune balance.</p><p><strong>Methods: </strong>The study included 145 participants divided into four groups: T2DM with nephropathy (35), T2DM without nephropathy (35), non-diabetic chronic kidney disease (ND-CKD) (35), and healthy controls (35). Various assessments were conducted, including anthropometric measurements, biochemical analyses, gene expression analysis was performed using RT-qPCR to profile mRNA and miRNA expression levels, flow cytometry (immune cell populations), and cytokine analysis by ELISA. Statistical analyses were carried out using SPSS, jamovi, Orange Data Mining, and Excel, ensuring robust evaluation and interpretation of the data.</p><p><strong>Results: </strong>Th9 cells correlated with IL-9 (<i>r</i> = 0.72, <i>p</i> < 0.01), and Treg cells with IL-10 (<i>r</i> = 0.68, <i>p</i> < 0.01). The Th9/Treg ratio significantly increased across groups (χ² = 14.8, <i>p</i> < 0.001), with notable differences between HC and T2DM (<i>p</i> = 0.009) and HC and DN (<i>p</i> < 0.001). IL-9 (AUC = 0.880) and Th9/Treg ratio (AUC = 0.762) showed potential as DN diagnostic markers. PTEN levels were reduced in DN and ND-CKD (<i>p</i> < 0.001, <i>p</i> = 0.017), while MMP2, hsa-miR-21-5p, and hsa-miR-181b-5p were elevated in disease groups (all <i>p</i> < 0.001), correlating with renal markers. COL4A4 was higher in DN vs. HC (<i>p</i> = 0.004), with PTEN downregulation linked to immune imbalance and fibrosis.</p><p><strong>Conclusion: </strong>Our study unveils immune cell and cytokine intricacies in DN. The high Th9/Treg ratio in T2DM and DN suggests immune tolerance loss, potentially influencing DN development. IL-9 and IL-10 display diagnostic potential. The Th9/Treg ratio and IL-9 serves as a discriminative diagnostic marker, particularly in DN. These insights offer avenues for early DN diagnosis and management.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"1-25"},"PeriodicalIF":4.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent respiratory papillomatosis: Immunological mechanisms involved in recurrence.","authors":"Katya Karen López-Aguilar, María Eugenia Vargas-Camaño, Fernando Lozano-Patiño, María Isabel Castrejón Vázquez","doi":"10.1080/08830185.2024.2425428","DOIUrl":"10.1080/08830185.2024.2425428","url":null,"abstract":"<p><p>Recurrent respiratory papillomatosis is a benign neoplastic pathology in children, young people, and adults. It causes a significant deterioration in the quality of life, with symptoms typically referred to as dysphonia and hoarseness. This disease, with variable clinical courses ranging from spontaneous resolution to dissemination of the lower airway or airway obstruction that puts the individual's life at risk, characteristically requires multiple surgical interventions. Therapy with adjuvant drugs does not yet prove the effectiveness necessary to limit the recurrence and need for surgical reoperation in this condition. The review aimed to synthesize the immunopathogenic mechanisms of relapse in recurrent respiratory papillomatosis published in the current literature and the immunological implication of risk factors and treatment.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":" ","pages":"113-126"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}