Immunobiology最新文献

{"title":"The safety and efficacy of tumor necrosis factor-alpha inhibitor on pregnancy outcomes in patients with unexplained recurrent miscarriage","authors":"Fangxiang Mu,&nbsp;Chen Wang,&nbsp;Lin Liu,&nbsp;Xianghui Zeng,&nbsp;Fang Wang","doi":"10.1016/j.imbio.2024.152808","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152808","url":null,"abstract":"<div><h3>Objectives</h3><p>Although tumor necrosis factor-alpha inhibitor (TNFi) treatment may improve pregnancy outcomes in unexplained recurrent miscarriage (URM) patients, evidence for its efficacy and safety is still insufficient. The goal of this study was to evaluate the efficacy and safety of TNFi on pregnancy outcomes in patients with URM.</p></div><div><h3>Methods</h3><p>This retrospective study was conducted at a single institution in China, involving 121 patients treated with TNFi for URM from 2019 to 2022. Patients enrolled were divided into treatment group (receiving TNFi and heparin therapy) and control group (receiving heparin therapy). The outcome variables were the 24-week live birth rate, miscarriage rate, ectopic pregnancy rate, neonatal outcomes, and adverse events.</p></div><div><h3>Results</h3><p>In our study, patients receiving TNFi treatment exhibited a significant increase in live birth rates, achieving 71.2 % compared to the 50.9 % observed in the control group (OR 2.507, 95 % CI: 1.127–5.579). Concurrently, there was a discernible reduction in the miscarriage rate within the TNFi-treated group, marking 24.2 %, in contrast to 43.6 % in the control group (OR 0.387, 95 % CI: 0.170–0.884). Subgroup analyses further illuminated that those under the age of 35 benefitted remarkably from TNFi treatment, with live birth rates soaring to 62.5 % (OR 2.525, 95 % CI: 1.041–6.125). For patients with a history of two miscarriages, the TNFi regimen significantly augmented the live birth rate to 58.9 % (OR 3.044, 95 % CI: 1.039–8.921). Patients with a normal weight range registered a 58.4 % live birth rate post-TNFi treatment (OR 4.261, 95 % CI: 1.539–11.397). Notably, an evident interaction between BMI and TNFi treatment was identified, suggesting a potential modulatory role of BMI on the therapeutic efficacy of TNFi. About safety assessments, neither the TNFi-treated group nor the control manifested any significant disparities in liver function abnormalities, platelet count anomalies, or other pregnancy-related complications.</p></div><div><h3>Conclusions</h3><p>TNFi, alongside basic therapy, notably enhances the live birth rate in URM patients under 35, with two prior miscarriages or a normal BMI, without increasing adverse event risk. Further prospective studies are essential to validate these observations.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152808"},"PeriodicalIF":2.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000263/pdfft?md5=47fe2a4a545794de69cd120b3ac46139&pid=1-s2.0-S0171298524000263-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909799","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":"The heterogeneity of tumour-associated macrophages contributes to the clinical outcomes and indications for immune checkpoint blockade in colorectal cancer patients","authors":"Junhui Tang ,&nbsp;Liang Ming ,&nbsp;Feiyu Qin ,&nbsp;Yan Qin ,&nbsp;Duo Wang ,&nbsp;Liuying Huang ,&nbsp;Yulin Cao ,&nbsp;Zhaohui Huang ,&nbsp;Yuan Yin","doi":"10.1016/j.imbio.2024.152805","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152805","url":null,"abstract":"<div><p>Tumor-associated macrophages (TAMs), one of the major immune cell types in colorectal cancer (CRC) tumor microenvironment (TME), play indispensable roles in immune responses against tumor progression. In this study, we aimed to know whether the extensive inter and intra heterogeneity of TAMs contributes to the clinical outcomes and indications for immune checkpoint blockade (ICB) in CRC. We used single-cell RNA sequencing (scRNA-Seq) data from 60 CRC patients and charactrized TAMs based on anatomic locations, tumor regions, stages, grades, metastatic status, MSS/MSI classification and pseudotemporal differentiation status. We then defined a catalog of 21 gene modules that determine macrophage status, and identified 7 of them as relevant to clinical outcomes and 11 as indications for ICB therapy. On this basis, we constructed a unique TAM subgroup profile, aiming to find features that may be highly responsive to immunotherapy for the CRC with poor prognosis under conventional treatment. This TAM subpopulation is enriched in tumors and is associated with poor prognosis, but exhibits a high immunotherapy response signature (HIM TAM). Further spatial transcriptome analysis and ligand-receptor interaction analysis confirmed that HIM TAM is involved in shaping TIME, especially the regulation of T cells. Our study provides insights into different TAM subtypes, highlights the importance of TAM heterogeneity in relation to patient prognosis and immunotherapy response, and reveals potential immunotherapy strategies based on TAM characteristics for CRC that does not respond well to conventional therapy.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152805"},"PeriodicalIF":2.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000238/pdfft?md5=685e3685df77a838f356fef60a790483&pid=1-s2.0-S0171298524000238-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140643768","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":"Increased co-expression of ICOS and PD-1 predicts poor overall survival in patients with acute myeloid leukemia","authors":"Shiyi Pan ,&nbsp;Qinghua Cai ,&nbsp;Yiqiong Wei ,&nbsp;Tang Haifeng ,&nbsp;Yuping Zhang ,&nbsp;Wei Zhou ,&nbsp;Tingfen Deng ,&nbsp;Wenjian Mo ,&nbsp;Shunqing Wang ,&nbsp;Caixia Wang ,&nbsp;Cunte Chen","doi":"10.1016/j.imbio.2024.152804","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152804","url":null,"abstract":"<div><h3>Background</h3><p>Inducible co-stimulatory factor (ICOS) has a dual role: activating cytotoxic T cells against tumors or exacerbating immunosuppression of regulatory T cells (Tregs) to participate in immune evasion. However, the correlation between ICOS and its co-expression with inhibitory immune checkpoints (IICs) and prognosis in acute myeloid leukemia (AML) is little known.</p></div><div><h3>Methods</h3><p>The prognostic importance of ICOS and IICs in 62 bone marrow (BM) samples of de novo AML patients from our clinical center (GZFPH) was explored and then the RNA sequencing data of 155 AML patients from the Cancer Genome Atlas (TCGA) database was used for validation.</p></div><div><h3>Results</h3><p>In both GZFPH and TCGA cohorts, high expression of ICOS was significantly associated with poor overall survival (OS) in patients with AML (<em>P</em> &lt; 0.05). Importantly, co-expression of ICOS and PD-1, PD-L1, PD-L2, CTLA-4, and LAG-3 predicted poor OS in AML; among them, ICOS/PD-1 was the optimal combination of immune checkpoints (ICs). The co-expression of ICOS and PD-1 was correlated with poor OS in non-acute promyelocytic leukemia (non-APL) patients following chemotherapy. Additionally, ICOS/PD-1 was an independent OS-predicting factor (<em>P</em> &lt; 0.05). Notably, a nomogram model was constructed by combining ICOS/PD-1, age, European Leukemia Net (ELN) risk stratification, and therapy to visually and personalized predict the 1-, 3-, and 5-year OS of patients with non-APL.</p></div><div><h3>Conclusion</h3><p>Increased expression of ICOS predicted poor outcomes, and ICOS/PD-1 was the optimal combination of ICs to predict outcomes in patients with AML, which might be a potential immune biomarker for designing novel AML therapy.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152804"},"PeriodicalIF":2.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000226/pdfft?md5=a41818c33f867a0053765c2149deef06&pid=1-s2.0-S0171298524000226-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140551740","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":"Alterations in the immune landscape characterized by inflammatory activation and immune escape within 12 h after trauma","authors":"Chenghu Song ,&nbsp;Weici Liu ,&nbsp;Yu Luo ,&nbsp;Jiwei Liu ,&nbsp;Guanyu Jiang ,&nbsp;Ruixin Wang ,&nbsp;Zhao He ,&nbsp;Xiaokun Wang ,&nbsp;Wenjun Mao","doi":"10.1016/j.imbio.2024.152801","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152801","url":null,"abstract":"<div><h3>Background</h3><p>Trauma is statistically a significant cause of mortality among patients across countries. Nevertheless, the precise correlation between genetic diagnostic markers and the intricate mechanism of trauma remains indistinct.</p></div><div><h3>Methods</h3><p>Our study exclusively centered on trauma patients and selected three trauma-related datasets from the Gene Expression Omnibus (GEO) database, all of which had blood samples collected within post-traumatic 12 h. Differential gene screening, the WGCNA and Cytoscape software were employed to analyze the two datasets, with a particular emphasis on the top 100 genes selected based on MCC algorithm scores. A logistic diagnostic model was constructed by analyzing the intersection genes in the third dataset, leading to the identification of diagnostic biomarkers with high efficiency. The global immune landscape of these patients was extensively investigated using a multidimensional approach. Meanwhile, the underlying pathological and physiological mechanisms associated with early trauma status are summarized by integrating existing literature.</p></div><div><h3>Results</h3><p>Out of these two GEO datasets, 21 overlapping genes were identified and incorporated into in the logistic diagnostic model constructed in the GSE36809 dataset. A panel of 9 genes was uncovered as a diagnostic biomarker, and their expression and correlation were subsequently verified. Additionally, by virtue of various algorithms, the findings revealed an upregulation of neutrophil expression and a downregulation of CD8+ T cell expression, indicating characteristic early trauma-induced inflammation activation and immune suppression. The correlation observed between the feature genes and immune cells serves to validate the exceptional diagnostic capability of these 9 genes in identifying trauma status and their promising potential for patients who could benefit from targeted immune interventions. Drawing from these findings, the discussion section offers insights into the underlying pathological and physiological mechanisms at play.</p></div><div><h3>Conclusion</h3><p>Our research has discovered a novel diagnostic biomarker and unveiled its association with post-traumatic immune alterations. This breakthrough enables accurate and timely diagnosis of early trauma, facilitating the implementation of appropriate healthcare interventions.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152801"},"PeriodicalIF":2.8,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000196/pdfft?md5=b31ee75ff4ec81e8d6eeea3663a806c7&pid=1-s2.0-S0171298524000196-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140537211","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":"LncRNA SNHG1 overexpression alleviates osteoarthritis via activating PI3K/Akt signal pathway and suppressing autophagy","authors":"Qiushi Wang,&nbsp;Jie Yang,&nbsp;Rui Pan,&nbsp;Zhengang Zha","doi":"10.1016/j.imbio.2024.152799","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152799","url":null,"abstract":"<div><p>We hereby intend to further explore and confirm the underlying mechanism of Small nucleolar RNA Host Gene 1 (SNHG1) in osteoarthritis (OA). For <em>in vitro</em> assays, OA was induced in primary chondrocytes with interleukin-1β (IL-1β) treatment; while for <em>in vivo</em> tests, OA model was established in mice using the destabilization of the medial meniscus (DMM) method. Cell viability and apoptosis were assessed with MTT and flow cytometry assays, respectively. Cartilage tissue was stained by Safranin-O/Fast Green Staining. The mRNA and protein levels were separately determined via quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. SNHG1 overexpression promoted the viability yet inhibited the apoptosis of chondrocytes injured by IL-1β. Moreover, the overexpression of SNHG1 promoted B-cell lymphoma-2 (Bcl-2) expression and activated phosphoinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway but suppressed the process of autophagy, which led to down-regulation of light chain 3 (LC3)-II/I level and up-regulation of P62 level. However, rapamycin (RAPA, an autophagy activator) and LY294002 (a PI3K inhibitor) reversed the effects of SNHG1 overexpression on the viability and apoptosis of chondrocytes as well as on the proteins related to PI3K/Akt pathway and autophagy. In OA-modeled mice, SNHG1 overexpression prevented the loss of chondrocytes via the activation of PI3K/Akt pathway and the suppression of autophagy. SNHG1 overexpression might inhibit the apoptosis of chondrocytes by promoting PI3K/Akt pathway and inhibiting autophagy.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152799"},"PeriodicalIF":2.8,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000172/pdfft?md5=71ea02c29534e067f3233b8b4ef54361&pid=1-s2.0-S0171298524000172-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559251","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":"Association of neutrophil extracellular trap levels with Raynaud’s phenomenon, glomerulonephritis and disease index score in SLE patients from Brazil","authors":"Eduardo Delabio Auer ,&nbsp;Valéria Bumiller-Bini Hoch ,&nbsp;Emiliano Borges da Silva ,&nbsp;Yohan Ricci Zonta ,&nbsp;Luciane Alarcão Dias-Melicio ,&nbsp;Thelma Larocca Skare ,&nbsp;Vanessa F. Picceli ,&nbsp;Iara José Messias-Reason ,&nbsp;Angelica Beate Winter Boldt","doi":"10.1016/j.imbio.2024.152803","DOIUrl":"10.1016/j.imbio.2024.152803","url":null,"abstract":"<div><p>Neutrophil extracellular traps (NETs) are cell-extruded DNA strands coated with neutrophils' nuclear proteins and enzymes from cytotoxic granules, produced by NETosis, a cell death pathway. They perform an important defensive role in innate immunity, but their increased production and/or inefficient degradation expose new antigens, such as DNA or citrullinated histone peptides, triggering autoimmunity. This study aimed to access possible associations between serum NETs levels with epidemiological, clinical, and serological data from a well-characterized SLE Brazilian patients’ cohort. NET levels were evaluated in one hundred seventy serum samples of patients with Systemic Lupus Erythematosus (SLE) using an Immunoassay. Univariate and multivariate binary logistic regression used clinical patients' data as independent variables. Parametric and non-parametric tests compared log10 base serum NET levels transformed between patients' groups. SLE patients were also dichotomized into “High serum NET levels” and “Low serum NET levels” groups. All analyses were performed in R language 4.1.2, and <em>p</em> &lt; 0.05 were considered significant. Increased susceptibility for high serum NET levels was observed in SLE patients with Raynaud's phenomenon (OR = 2.30, 95 % CI = 1.06–5.21 and <em>p</em> = 0.039), independently of any other risk factor. Also, SLE patients with Raynaud's phenomenon presented higher mean NET serum levels (mean = −0.13 vs. −0.51, <em>p</em> = 0.01). In addition, higher mean NET serum levels were associated with glomerulonephritis (mean = -0.45 vs. −0.12, <em>p</em> = 0.03). Ultimately, the SLEDAI index scored higher in the high NETs serum levels group (median = 2.0 vs. 0.0, <em>p</em> = 6 × 10⁻³). The formation of NETs might be implicated in Raynaud's phenomenon, glomerulonephritis, and disease index score in SLE patients. Our results highlight the importance of serum NET levels as a possible therapeutical target to modulate the clinical course of SLE.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152803"},"PeriodicalIF":2.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000214/pdfft?md5=2e87b717ec774929921c1e0a21e8600c&pid=1-s2.0-S0171298524000214-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613605","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":"PSMC2 promotes glioma progression by regulating immune microenvironment and PI3K/AKT/mTOR pathway","authors":"Yizheng Wang ,&nbsp;Shiyang Zhang ,&nbsp;Zijun Zhao ,&nbsp;Qianxu Jin ,&nbsp;Zairan Wang ,&nbsp;Zihan Song ,&nbsp;Liqiang Liu ,&nbsp;Zongmao Zhao","doi":"10.1016/j.imbio.2024.152802","DOIUrl":"https://doi.org/10.1016/j.imbio.2024.152802","url":null,"abstract":"<div><h3>Background</h3><p>Glioma, the most frequent and malignant central nervous system (CNS) cancer, has a bad outcome. Proteasome 26S subunit ATPase 2 (PSMC2) is an essential part of the 26S proteasome and promotes the development of several tumors. However, the pathway and function of PSMC2 in glioma have not been unelucidated.</p></div><div><h3>Methods</h3><p>This study analyzed PSMC2 expression in glioma tissues and its predictive significance for patients. We examined the link between PSMC2 and DNA methylation, immune cell infiltration, tumor immune cycle, immune cell homeostasis, and immune checkpoints. Subsequently, immunohistochemistry and in vitro trials were employed to validate the expression, prognostic potential, and function of PSMC2 in glioma. The mechanisms of PSMC2 in glioma were further explored.</p></div><div><h3>Results</h3><p>Our study revealed that PSMC2 expression increased in glioma tissues contrasted with healthy tissues, and patients with high PSMC2 glioma exhibited poor overall survival (OS) compared to the low-PSMC2 group. Immune profile analysis revealed that PSMC2 was positively related to immunosuppressive cell infiltration and immune checkpoints and adversely related to the cancer immune cycle and immune cell homeostasis. In cell-based investigations, the inhibition of PSMC2 was found to effectively suppress the aggressiveness and proliferation of glioma cell lines while also enhancing cell cycle arrest and promoting cell death. Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and in vitro experiments showed that PSMC2 promoted glioma development through the PI3K/AKT/mTOR pathway.</p></div><div><h3>Conclusions</h3><p>PSMC2 was upregulated in glioma and promoted cancer progression by modulating the tumor immune microenvironment, cancer cell biological behavior, immune cell homeostasis, and the PI3K/AKT/mTOR pathway, providing a new option to treat glioma.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152802"},"PeriodicalIF":2.8,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000202/pdfft?md5=2a1cf96018cd94641396b034b544da06&pid=1-s2.0-S0171298524000202-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140342312","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":"The changes of intestinal flora and its relevance with memory Tfh and B cells in rheumatoid arthritis patients treated with csDMARDs and csDMARDs + bDMARDs","authors":"Chunlei Jiang ,&nbsp;Shuhong Chi ,&nbsp;Fengkui Wang ,&nbsp;Chenyang Zhao ,&nbsp;Xiaojuan Yang ,&nbsp;Miao Liu ,&nbsp;Bin Ma ,&nbsp;Jian Chen ,&nbsp;Chunxia Su ,&nbsp;Xiangguo Duan","doi":"10.1016/j.imbio.2024.152798","DOIUrl":"10.1016/j.imbio.2024.152798","url":null,"abstract":"<div><h3>Background</h3><p>A growing body of experimental and clinical evidence has implicated gut microbiota in the onset and course of rheumatoid arthritis (RA). The imbalance of intestinal flora in RA patients may lead to abnormal expression of immune cells and related cytokines.</p></div><div><h3>Purpose</h3><p>Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and conventional synthetic disease-modifying antirheumatic drugs combined with biological disease-modifying antirheumatic drugs (csDMARDs + bDMARDs) are widely used to treat RA, but the characteristics of gut microbiota before and after treatment and their relationship with memory Tfh/B cells and cytokines remain unclear.</p></div><div><h3>Methods</h3><p>Stool samples were collected from 50 RA patients and 25 healthy controls (HCs) for 16SrRNA gene sequencing. We examined the proportion of lymphocyte subsets in healthy controls and RA patients. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of related cytokines in serum. The α and β diversity of intestinal flora, and the correlation between intestinal flora and clinical indicators, lymphocyte subsets, cytokines were analyzed.</p></div><div><h3>Result</h3><p>At the genus level, Ruminococcaceae_Ruminococcus was decreased in the csDMARDs and csDMARDs + bDMARDs treatment group, whereas Faecalibacterium was reduced in the csDMARDs treatment group, compared to untreated group. CD4⁺CD45RO⁺CCR7⁺CXCR5⁺central memory Tfh cells and CD4⁺CD45RO⁺CCR7^-CXCR5⁺effector memory Tfh cells were significantly lower in the csDMARDs + bDMARDs treatment group than in untreated group. CD19⁺CD27⁺IgD⁺pre-switched memory B cells were higher in the csDMARDs and csDMARDs + bDMARDs treatment groups, whereas CD19⁺CD27⁺IgD^-switched memory B cells were significantly lower than in untreated group. Ruminococcaceae_Ruminococcus was negatively correlated with CD19⁺CD27⁺IgD⁺ pre-switched memory B cells but positively correlated with CD4⁺CD45RO⁺CCR7^-CXCR5⁺effector memory Tfh and CD19⁺CD27⁺IgD^-switched memory B cells in patients with RA treated with DMARDs.</p></div><div><h3>Conclusion</h3><p>The gut microbiota, memory Tfh cells, memory B cells, and cytokines of patients with RA changed significantly under different treatment regimens and had certain correlations with the clinical indicators of RA.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152798"},"PeriodicalIF":2.8,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000160/pdfft?md5=830235ff7c7dafc5ad593cdb26294649&pid=1-s2.0-S0171298524000160-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140282134","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":"Effect of dapagliflozin on collectins and complement activation in plasma from patients with type 2 diabetes and albuminuria: Data from the DapKid cohort","authors":"Mia Jensen ,&nbsp;Mie K. Eickhoff ,&nbsp;Frederik Persson ,&nbsp;Peter Rossing ,&nbsp;Steffen Thiel ,&nbsp;Søren W.K. Hansen ,&nbsp;Yaseelan Palarasah ,&nbsp;Per Svenningsen ,&nbsp;Boye L. Jensen","doi":"10.1016/j.imbio.2024.152797","DOIUrl":"10.1016/j.imbio.2024.152797","url":null,"abstract":"<div><h3>Background</h3><p>Sodium-glucose cotransporter 2 (SGLT- 2) inhibitors exert cardiovascular and kidney-protective effects in people with diabetes. Attenuation of inflammation could be important for systemic protection. The lectin pathway of complement system activation is linked to diabetic nephropathy. We hypothesized that SGLT-2 inhibitors lower the circulating level of pattern-recognition molecules of the lectin cascade and attenuate systemic complement activation.</p></div><div><h3>Methods</h3><p>Analysis of paired plasma samples from the DapKid crossover intervention study where patients with type 2 diabetes mellitus (T2DM) and albuminuria were treated with dapagliflozin and placebo for 12 weeks (10 mg/day, n=36). ELISA was used to determine concentrations of collectin kidney 1 (CL-K1), collectin liver 1 (CL-L1), mannose-binding lectin (MBL), MBL-associated serine protease 2 (MASP-2), the anaphylatoxin complement factor 3a (C3a), the stable C3 split product C3dg and the membrane attack complex (sC5b-9).</p></div><div><h3>Results</h3><p>As published before, dapagliflozin treatment lowered Hba_1C from 74 (14.9) mmol/mol to 66 (13.9) mmol/mol (p&lt;0.0001), and the urine albumin/creatinine ratio from 167.8 mg/g to 122.5 mg/g (p&lt;0.0001). Plasma concentrations of CL-K1, CL-L1, MBL, and MASP-2 did not change significantly after dapagliflozin treatment (P&gt;0.05) compared to placebo treatment. The plasma levels of C3a (P&lt;0.05) and C3dg (P&lt;0.01) increased slightly but significantly, 0.6 [0.2] units/mL and 76 [52] units/mL respectively, after dapagliflozin treatment. The C9-associated neoepitope in C5b-9 did not change in plasma concentration by dapagliflozin (P&gt;0.05).</p></div><div><h3>Conclusion</h3><p>In patients with type 2 diabetes and albuminuria, SGLT-2 inhibition resulted in modest C3 activation in plasma, likely not driven by primary changes in circulating collectins and not resulting in changes in membrane attack complex. Based on systemic analyses, organ-specific local protective effects of gliflozins against complement activation cannot be excluded.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152797"},"PeriodicalIF":2.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000159/pdfft?md5=c412cbc6629b0d43b57c13f30c145a8a&pid=1-s2.0-S0171298524000159-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140181910","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":"Transcription suppression of GABARAP mediated by lncRNA XIST-EZH2 interaction triggers caspase-11-dependent inflammatory injury in ulcerative colitis","authors":"Dan Gu ,&nbsp;Ting Cao ,&nbsp;Shijie Yi ,&nbsp;Xiaoqian Li ,&nbsp;Ya Liu","doi":"10.1016/j.imbio.2024.152796","DOIUrl":"10.1016/j.imbio.2024.152796","url":null,"abstract":"<div><h3>Background</h3><p>We have previously found that enhancer of zeste homolog 2 (EZH2) is correlated with inflammatory infiltration and mucosal cell injury in ulcerative colitis (UC). This study aims to analyze the role of X-inactive specific transcript (XIST), a possible interactive long non-coding RNA of EZH2, in UC and to explore the mechanisms.</p></div><div><h3>Methods</h3><p>C57BL/6N mice were treated with dextran sulfate sodium (DSS), and mouse colonic mucosal epithelial cells were treated with DSS and lipopolysaccharide (LPS) for UC modeling. The UC-related symptoms in mice, and the viability and apoptosis of mucosal epithelial cells were determined. Inflammatory injury in animal and cellular models were assessed through the levels of ACS, occludin, IL-1β, IL-18, TNF-α, caspase-1, and caspase-11. Molecular interactions between XIST, EZH2, and GABA type A receptor-associated protein (GABARAP) were verified by immunoprecipitation assays, and their functions in inflammatory injury were determined by gain- or loss-of-function assays.</p></div><div><h3>Results</h3><p>XIST was highly expressed in DSS-treated mice and in DSS + LPS-treated mucosal epithelial cells. It recruited EZH2, which mediated gene silencing of GABARAP through H3K27me3 modification. Silencing of XIST alleviated body weight loss, colon shortening, and disease active index of mice and reduced inflammatory injuries in their colon tissues. Meanwhile, it reduced apoptosis and inflammation in mucosal epithelial cells. However, these alleviating effects were blocked by either EZH2 overexpression or GABARAP knockdown. Rescue experiments identified caspase-11 as a key effector mediating the inflammatory injury following GABARAP loss.</p></div><div><h3>Conclusion</h3><p>This study suggests that the XIST-EZH2 interaction-mediated GABARAP inhibition activates caspase-11-dependent inflammatory injury in UC.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 3","pages":"Article 152796"},"PeriodicalIF":2.8,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000147/pdfft?md5=b60fa3a4a6fe804afbff7824d492d409&pid=1-s2.0-S0171298524000147-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140054399","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}