Immunology letters最新文献

{"title":"Type 1 Diabetes Brazilian patients exhibit reduced frequency of recent thymic emigrants in regulatory CD4+CD25+Foxp3+T cells","authors":"Jeane de Souza Nogueira ,&nbsp;Thamires Rodrigues Gomes ,&nbsp;Danielle Angst Secco ,&nbsp;Inez Silva de Almeida ,&nbsp;Alessandra Saldanha Matheus Fernandes da Costa ,&nbsp;Roberta Arnoldi Cobas ,&nbsp;Gilson Costa dos Santos Jr ,&nbsp;Marília Brito Gomes ,&nbsp;Luís Cristóvão Porto","doi":"10.1016/j.imlet.2024.106857","DOIUrl":"https://doi.org/10.1016/j.imlet.2024.106857","url":null,"abstract":"<div><p>To control immune responses, regulatory CD4⁺CD25⁺Foxp3⁺ T cells (Treg) maintain their wide and diverse repertoire through continuous arrival of recent thymic emigrants (RTE). However, during puberty, the activity of RTE starts to decline as a natural process of thymic involution, introducing consequences, not completely described, to the repertoire. Type 1 diabetes (T1D) patients show quantitative and qualitative impairments on the Treg cells. Our aim was to evaluate peripheral Treg and RTE cell frequencies, in T1D patients from two distinct age groups (young and adults) and verify if HLA phenotypes are concomitant associated. To this, blood samples from Brazilian twenty established T1D patients (12 young and 8 adults) and twenty-one healthy controls (11 young and 10 adults) were analyzed, by flow cytometry, to verify the percentages of CD4, Treg (CD4⁺CD25⁺Foxp3⁺) and the subsets of CD45RA⁺ (naive) and CD31⁺(RTE) within then. Furthermore, the HLA typing was also set. We observed that the young established T1D patients feature decreased frequencies in total Treg cells and naive RTE within Treg cells. Significant prevalence of HLA alleles, associated with risk, in T1D patients, was also identified. Performing a multivariate analysis, we confirmed that the cellular changes described offers significant variables that distinct T1D patients from the controls. Our data collectively highlight relevant aspects about homeostasis imbalances in the Treg cells of T1D patients, especially in young, and disease prognosis; that might contribute for future therapeutic strategies involving Treg cells manipulation.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621772","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":"Endoplasmic reticulum stress response in immune cells contributes to experimental autoimmune encephalomyelitis pathogenesis in rats","authors":"Sasenka Vidicevic ,&nbsp;Jelena Tasic ,&nbsp;Zeljka Stanojevic ,&nbsp;Darko Ciric ,&nbsp;Tamara Martinovic ,&nbsp;Verica Paunovic ,&nbsp;Sasa Petricevic ,&nbsp;Nina Tomonjic ,&nbsp;Aleksandra Isakovic ,&nbsp;Vladimir Trajkovic","doi":"10.1016/j.imlet.2024.106855","DOIUrl":"10.1016/j.imlet.2024.106855","url":null,"abstract":"<div><p>We examined the role of endoplasmic reticulum (ER) stress and the ensuing unfolded protein response (UPR) in the development of the central nervous system (CNS)-directed immune response in the rat model of experimental autoimmune encephalomyelitis (EAE). The induction of EAE with syngeneic spinal cord homogenate in complete Freund's adjuvant (CFA) caused a time-dependent increase in the expression of ER stress/UPR markers glucose-regulated protein 78 (GRP78), X-box-binding protein 1 (XBP1), C/EBP homologous protein (CHOP), and phosphorylated eukaryotic initiation factor 2α (eIF2α) in the draining lymph nodes of both EAE-susceptible Dark Agouti (DA) and EAE-resistant Albino Oxford (AO) rats. However, the increase in ER stress markers was more pronounced in AO rats. CFA alone also induced ER stress, but the effect was weaker and less sustained compared to full immunization. The ultrastructural analysis of DA lymph node tissue by electron microscopy revealed ER dilatation in lymphocytes, macrophages, and plasma cells, while immunoblot analysis of CD3-sorted lymph node cells demonstrated the increase in ER stress/UPR markers in both CD3⁺ (<em>T</em> cell) and CD3⁻ (non-T) cell compartments. A positive correlation was observed between the levels of ER stress/UPR markers in the CNS-infiltrated mononuclear cells and the clinical activity of the disease. Finally, the reduction of EAE clinical signs by ER stress inhibitor ursodeoxycholic acid was associated with the decrease in the expression of mRNA encoding pro-inflammatory cytokines TNF and IL-1β, and encephalitogenic <em>T</em> cell cytokines IFN-γ and IL-17. Collectively, our data indicate that ER stress response in immune cells might be an important pathogenetic factor and a valid therapeutic target in the inflammatory damage of the CNS.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305506","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":"Dual drug nanoparticle synergistically induced apoptosis, suppressed inflammation, and protected autophagic response in rheumatoid arthritis fibroblast-like synoviocytes","authors":"Prakash Haloi ,&nbsp;Rajat Choudhary ,&nbsp;B. Siva Lokesh ,&nbsp;V. Badireenath Konkimalla","doi":"10.1016/j.imlet.2024.106854","DOIUrl":"10.1016/j.imlet.2024.106854","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is a chronic immune-mediated joint inflammatory disorder associated with aberrant activation of fibroblast-like synoviocytes (FLS). Recently, FLS gained importance due to its crucial role in RA pathogenesis, and thus, targeting FLS is suggested as an attractive treatment strategy for RA. FLS-targeted approaches may be combined with disease-modifying antirheumatic drugs (DMARDs) and natural phytochemicals to improve efficacy in RA control and negate immunosuppression. In this study, we assessed the therapeutic effectiveness of DD NP HG in primary RA-FLS cells isolated from the synovial tissue of FCA-induced RA rats. We observed that DD NP HG had good biosafety for healthy FLS cells and, at higher concentrations, a mild inhibitory effect on RA-FLS. The combination therapy (DD NP HG) of MTX NP and PEITC NE in RA-FLS showed a higher rate of apoptosis with significantly reduced LPS-induced expression of pro-inflammatory cytokines (TNF-α, IL-17A, and IL-6) in arthritic FLS. Further, the gene expression studies showed that DD NP HG significantly down-regulated the mRNA expression of <em>IL-1β, RANKL, NFATc1, DKK1, Bcl-xl, Mcl-1, Atg12,</em> and <em>ULK1,</em> and up-regulated the mRNA expression of <em>OPG, PUMA, NOXA</em> and <em>SQSTM1</em> in LPS-stimulated RA-FLS cells. Collectively, our results demonstrated that DD NP HG significantly inhibited the RA-FLS proliferation <em>via</em> inducing apoptosis, down-regulating pro-inflammatory cytokines, and further enhancing the expression of genes associated with bone destruction in RA pathogenesis. A nanotechnology approach is a promising strategy for the co-delivery of dual drugs to regulate the RA-FLS function and achieve synergistic treatment of RA.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305505","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":"Conventional dendritic cells 2, the targeted antigen-presenting-cell, induces enhanced type 1 immune responses in mice immunized with CVC1302 in oil formulation","authors":"Luping Du ,&nbsp;Haiyan Lu ,&nbsp;Xuwen Qiao ,&nbsp;Yuanpeng Zhang ,&nbsp;Liting Hou ,&nbsp;Xiaoming Yu ,&nbsp;Haiwei Cheng ,&nbsp;Jin Chen ,&nbsp;Qisheng Zheng ,&nbsp;Jibo Hou ,&nbsp;Guangzhi Tong","doi":"10.1016/j.imlet.2024.106856","DOIUrl":"10.1016/j.imlet.2024.106856","url":null,"abstract":"<div><p>Multifunctional CD4⁺ T helper 1 (Th1) cells, producing IFN-γ, TNF-α and IL-2, define a correlate of vaccine-mediated protection against intracellular infection. In our previous study, we found that CVC1302 in oil formulation promoted the differentiation of IFN-γ⁺/TNF-α⁺/IL-2⁺Th1 cells. In order to extend the application of CVC1302 in oil formulation, this study aimed to elucidate the mechanism of action in improving the Th1 immune response. Considering the signals required for the differentiation of CD4⁺ T cells to Th1 cells, we detected the distribution of innate immune cells and the model antigen OVA-FITC in lymph node (LN), as well as the quantity of cytokines produced by the innate immune cells. The results of these experiments show that, cDC2 and OVA-FITC localized to interfollicular region (IFR) of the draining lymph nodes, inflammatory monocytes localized to both IFR and T cell zone, which mainly infiltrate from the blood. In this inflammatory niche within LN, CD4⁺ T cells were attracted into IFR by CXCL10, secreted by inflammatory monocytes, then activated by cDC2, secreting IL-12. Above all, CVC1302 in oil formulation, on the one hand, targeted antigen and inflammatory monocytes into the LN IFR in order to attract CD4⁺ T cells, on the other hand, targeted cDC2 to produce IL-12 in order to promote optimal Th1 differentiation. The new finding will provide a blueprint for application of immunopotentiators in optimal formulations.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305504","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":"Corrigendum to ’ Aged AβPPswe/PS1ΔE9 mice as a useful animal model for studying the link between immunological senescence and diseases’[Immunol Lett. 2024 Feb 12:266:106842]","authors":"Jing Luan ,&nbsp;Na Guo ,&nbsp;Fengrui Hu ,&nbsp;Xingchun Gou ,&nbsp;Lixian Xu","doi":"10.1016/j.imlet.2024.106850","DOIUrl":"10.1016/j.imlet.2024.106850","url":null,"abstract":"","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000245/pdfft?md5=1296d72e78ace07a61faf485044283d5&pid=1-s2.0-S0165247824000245-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner","authors":"Da Liu ,&nbsp;Lang Hu ,&nbsp;Yue Yang ,&nbsp;Yina Wang ,&nbsp;Yayong Li ,&nbsp;Jing Su ,&nbsp;Guyi Wang ,&nbsp;Subo Gong","doi":"10.1016/j.imlet.2024.106853","DOIUrl":"10.1016/j.imlet.2024.106853","url":null,"abstract":"<div><h3>Background</h3><p>Allergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms.</p></div><div><h3>Methods</h3><p>First, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16 s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3.</p></div><div><h3>Results</h3><p>S. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16 s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury.</p></div><div><h3>Conclusions</h3><p>S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184281","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":"Brain inflammation in experimental autoimmune encephalomyelitis induced in Dark Agouti rats with spinal cord homogenate","authors":"Goran Stegnjaić ,&nbsp;Bojan Jevtić ,&nbsp;Milica Lazarević ,&nbsp;Đurđica Ignjatović ,&nbsp;Mirko Tomić ,&nbsp;Neda Nikolovski ,&nbsp;Ivana Bjelobaba ,&nbsp;Miljana Momčilović ,&nbsp;Mirjana Dimitrijević ,&nbsp;Đorđe Miljković ,&nbsp;Suzana Stanisavljević","doi":"10.1016/j.imlet.2024.106852","DOIUrl":"10.1016/j.imlet.2024.106852","url":null,"abstract":"<div><p>We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund's adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of <em>T</em> and <em>B</em> cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and β-synuclein was detected. Having in mind that reactivity against β-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. <em>T</em> cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174523","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":"Alendronate modulates cytokine responses in healthy young individuals after BCG vaccination","authors":"Ozlem Bulut ,&nbsp;Gizem Kilic ,&nbsp;Priya A. Debisarun ,&nbsp;Rutger Jan Röring ,&nbsp;Sarah Sun ,&nbsp;Manon Kolkman ,&nbsp;Esther van Rijssen ,&nbsp;Jaap ten Oever ,&nbsp;Hans Koenen ,&nbsp;Luis Barreiro ,&nbsp;Jorge Domínguez-Andrés ,&nbsp;Mihai G. Netea","doi":"10.1016/j.imlet.2024.106851","DOIUrl":"10.1016/j.imlet.2024.106851","url":null,"abstract":"<div><p>Bacillus Calmette–Guérin (BCG) vaccination induces memory characteristics in innate immune cells and their progenitors, a process called <em>trained immunity</em> mediated by epigenetic and metabolic reprogramming. Cholesterol synthesis plays an amplifying role in trained immunity through mevalonate release. Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, can inhibit cholesterol synthesis. We explored their effects on trained immunity induced by BCG in a placebo-controlled clinical study (NL74082.091.20) in young, healthy individuals. Participants receiving single-dose oral alendronate on the day of BCG vaccination had more neutrophils and plasma cells one month after treatment. Alendronate led to reduced proinflammatory cytokine production by PBMCs stimulated with heterologous bacterial and viral stimuli one month later. Furthermore, the addition of alendronate transcriptionally suppressed multiple immune response pathways in PBMCs upon stimulation. Our findings indicate that N-BPs modulate the long-lasting effects of BCG vaccination on the cytokine production capacity of innate immune cells.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000257/pdfft?md5=36864522947e00471d272443311e35ea&pid=1-s2.0-S0165247824000257-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to Macrophage-derived inflammation promotes pulmonary vascular remodeling in hypoxia-induced pulmonary arterial hypertension mice [Immunology Letters 263 (2023) 113–122 /IMLET_6819]","authors":"Hong Liu","doi":"10.1016/j.imlet.2024.106843","DOIUrl":"https://doi.org/10.1016/j.imlet.2024.106843","url":null,"abstract":"","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000178/pdfft?md5=6cf46251704681dcf6cc55699142eff6&pid=1-s2.0-S0165247824000178-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139936592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aged AβPPswe/PS1ΔE9 mice as a useful animal model for studying the link between immunological senescence and diseases","authors":"Jing Luan ,&nbsp;Na Guo ,&nbsp;Fengrui Hu ,&nbsp;Xingchun Gou ,&nbsp;Lixian Xu","doi":"10.1016/j.imlet.2024.106842","DOIUrl":"10.1016/j.imlet.2024.106842","url":null,"abstract":"<div><p>The <em>APPswe/PS1</em><strong>Δ</strong><em>E9</em> mouse is a double transgenic murine model that harbors two transgenes for Alzheimer's Disease (AD)-related mutant proteins. We previously discovered that this double transgenic animal had a premature immunosenescence phenotype. However, it is unclear how this phenotype progresses to a later stage. This study aimed to elucidate the changes in systemic characteristics aside from those associated with AD between elderly <em>APPswe/PS1</em><strong>Δ</strong><em>E9</em> mice and littermate control wild-type mice. Tumors in all organs were considerably more frequent in AD mice aged 24 months than in the control wild-type mice. In addition, the survival rate of aged AD mice was considerably lower than that of wild-type control mice. Further, we discovered that the phenotypic difference was mainly caused by severe immunological aging, as evidenced by a high proportion of exhausted T lymphocytes in AD mice compared to wild-type mice of the same age. Based on our findings, the harm produced by normal aging is not as severe as immunological senescence. Addressing immunological aging, as opposed to anti-aging alone, may be a more crucial target for a long life free of cancer.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735091","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}