Critical reviews in immunology最新文献

{"title":"The Combined Administration of Disulfiram and Baicalin Alleviates Membranous Nephropathy by Inhibiting Podocyte Inflammation and Pyroptosis.","authors":"Chengli Lou, Yijing Zhou, Bo Feng, Xiaoping Fan, Xiuqin Xu, Pingxin Hu, Xiangjing Wang","doi":"10.1615/CritRevImmunol.2026062334","DOIUrl":"10.1615/CritRevImmunol.2026062334","url":null,"abstract":"<p><strong>Background: </strong>Membranous nephropathy (MN) is an autoimmune kidney disease, and its pathogenesis is related to inflammation and podocyte injury. Both disulfiram and baicalin can relieve the symptoms of MN through anti-inflammatory effects. However, it is still unclear whether disulfiram and baicalin can enhance the therapeutic effect of MN by combination therapy.</p><p><strong>Methods: </strong>We screened the optimal drug concentration of disulfiram and baicalin for incubation of AB8/13 cells by CCK-8 assay. Angiotensin II was used to stimulate AB8/13 cells to construct a MN cell model. Subsequently, cell proliferation assays, network pharmacology analysis, ELISA assay, and pyroptosis detection were employed to investigate the effects of disulfiram combined with baicalin in MN.</p><p><strong>Results: </strong>Firstly, 250 nM disulfiram and 5 μmol/L baicalin were selected as the optimal dose for the treatment of MN. Cell proliferation assay showed that the combined administration of disulfiram and baicalin could reduce Angiotensin II-induced podocyte injury. Subsequently, a total of 129 genes were identified as potential therapeutic targets of the combination therapy involving disulfiram and baicalin for MN. These targets mainly focused on regulating inflammatory-related functions and pathways. Disulfiram combined with baicalin inhibited the inflammation of MN by suppressing the levels of TNF-α, IL-8 and C-reactive protein and promoting the levels of TGF-β and IL-10. Disulfiram combined with baicalin significantly attenuated Angiotensin II-induced podocyte pyroptosis, as indicated by reduction of Caspase-1 and GSDMD-N, lactate dehydrogenase release and the percentage of podocytes stained with propidium iodide.</p><p><strong>Conclusion: </strong>Compared with monotherapy using either disulfiram or baicalin alone for MN, the combination has a protective role in podocyte injury by inhibiting inflammation and pyroptosis. This discovery provides a new perspective for clarifying the pharmacological effects of disulfiram and baicalin to podocyte injury in MN.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 1","pages":"73-84"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Ursolic Acid and Rosuvastatin Treatment Mitigates Inflammation and Oxidative Stress in Diabetic Nephropathy Model Cells.","authors":"Yijing Zhou, Chengli Lou, Xiangjing Wang, Pingxin Hu, Xiuqin Xu","doi":"10.1615/CritRevImmunol.2026061077","DOIUrl":"10.1615/CritRevImmunol.2026061077","url":null,"abstract":"<p><strong>Background: </strong>Ursolic acid (UA) and Rosuvastatin (RST) improves diabetic nephropathy (DN). However, the combination therapy of UA and RST on DN and its possible mechanism requires exploration.</p><p><strong>Methods: </strong>Streptozotocin (STZ)-induced DN model cells were treated with UA and RST alone or in combination. Cell viability and apoptosis were assessed using Cell Counting Kit-8 (CCK-8), flow cytometry, and TUNEL staining. The inflammation-related factors' release was examined by enzyme linked immunosorbent assay (ELISA). Potential mechanism was analyzed through network pharmacology. The reactive oxygen species (ROS) accumulation was detected using flow cytometry. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) were measured using commercial reagent kits.</p><p><strong>Results: </strong>UA and RST increased viability while reducing apoptosis of STZ-induced cells. UA and RST suppressed the release of inflammation-related factors in STZ-induced cells. Through network pharmacology analysis, the inflammation and oxidative stress were thought to be implicated in the treatment of UA and RST in DN. UA and RST downregulated ROS and MDA while upregulating SOD and CAT in STZ-induced cells. Compared with RST and UA used individually, their combination showed a more potent effect in increasing viability, mitigating apoptosis, and suppressing the inflammation and oxidative stress in STZ-induced cells.</p><p><strong>Conclusion: </strong>Combined UA and RST therapy ameliorated the inflammation and oxidative stress in DN model cells, providing the theoretical basis for pharmacological research of DN.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 1","pages":"59-72"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Label-Free Impedance-Based Real-Time Cell Analysis Platform: An Advanced Technology Designed to Monitor the Cytotoxic Activity of Natural Killer Cells.","authors":"Kawaljit Kaur","doi":"10.1615/CritRevImmunol.2025061706","DOIUrl":"https://doi.org/10.1615/CritRevImmunol.2025061706","url":null,"abstract":"<p><p>Natural killer (NK) cells play a key role in targeting cancer, virus-infected, and senescent cells through direct cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC). Monitoring NK cell cytotoxicity is crucial for evaluating immune function, tracking disease progression, and assessing therapeutic outcomes, particularly in oncology and immunology. NK cells help manage infections, cancer, and other health conditions through their cytotoxic actions. Changes in NK activity can signal disease states or responses to treatments. NK cell-based therapies require functional assessments to maximize effectiveness. Abnormal NK cytotoxicity may be linked to autoimmune diseases or immune exhaustion in tumor microenvironments. Various methods are used to measure NK cell cytotoxicity, with the chromium-51 release assay once being the gold standard by detecting radioactive chromium release upon target cell destruction. This report highlights the significant potential of a label-free impedance-based Real Time Cell Analysis (RTCA) platform with complementary live cell imaging capability for label-free, dynamic monitoring of NK-target cell interactions over time.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 4","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NK Cells In Endocrine Autoimmune Disorders: Current Knowledge and Implications for Therapeutic Strategies.","authors":"Dorsa Iraji, Thea Sjøgren, Bergithe E Oftedal","doi":"10.1615/CritRevImmunol.2026062734","DOIUrl":"https://doi.org/10.1615/CritRevImmunol.2026062734","url":null,"abstract":"<p><p>Natural killer (NK) cells play critical roles in innate immunity and in shaping adaptive immune responses. Recent studies reveal their dual role in autoimmunity, either with a protective role by eliminating autoreactive cells or as contributors to pathogenic inflammation. This review summarizes current understanding of NK cell biology in endocrine autoimmune diseases, focusing on what is known for type 1 diabetes and autoimmune adrenal failure-Addison's disease. We further discuss emerging therapeutic approaches focusing on cytokine-activated (supercharged) NK cells and CAR NK cells, and highlight knowledge gaps and future priorities.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 4","pages":"75-86"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward a Unified Multidimensional HIV Cure: Integrating Virologic, Clinical, and Immunologic Perspectives.","authors":"Seyi Samson Enitan, Chukwudi Amaechi Ofodile, Richard Yomi Akele, Ayodeji Olusola Olayanju, Okeoghene Marcel Edafetanure-Ibeh, Grace Eleojo Itodo, Chinedu-Madu Jane Ugochi, Nnaji Joseph Chima, Chukwuma J Okafor, Comfort Bosede Enitan, Roselene Nmesoma Odimgbe","doi":"10.1615/CritRevImmunol.2026064384","DOIUrl":"https://doi.org/10.1615/CritRevImmunol.2026064384","url":null,"abstract":"<p><p>Despite major advances in antiretroviral therapy (ART), a definitive cure for human immunodeficiency virus (HIV) remains elusive. This review aims to propose a unified, multidimensional framework for HIV cure that integrates virologic, immunologic, and clinical perspectives to guide future research and therapeutic strategies. A structured narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar to identify relevant literature on HIV cure research. Articles published primarily between 2008 and 2026 were screened based on relevance, scientific rigor, and contribution to key themes. Findings were synthesized qualitatively to provide an integrated overview of emerging concepts, persistent challenges, and future directions in HIV cure research. Effective HIV cure strategies must integrate three interconnected dimensions: (1) virologic cure through durable suppression or elimination of replication-competent virus, (2) clinical cure through sustained remission without antiretroviral therapy (ART), and (3) immunologic cure through restoration of functional immune competence and inflammatory homeostasis. Current and emerging approaches, including latency-targeting agents, broadly neutralizing antibodies, therapeutic vaccines, immune modulators, and gene-editing technologies, demonstrate potential to bridge viral suppression with immune-mediated control. However, critical challenges persist, including reservoir heterogeneity, immune senescence, viral diversity, and the absence of standardized immunologic metrics. Proposed endpoints extend beyond CD4+ T cell counts to functional T cell responses, immune memory restoration, and normalization of inflammatory profiles. An effective HIV cure must integrate viral suppression, immune restoration, and functional remission. This unified, multidimensional framework provides a foundation for next-generation therapeutic strategies and clinical trial design aimed at achieving durable, host-mediated control.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 3","pages":"57-78"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIHA2 Promotes Hepatocellular Carcinoma Progression by Mediating Ubiquitination and Degradation of DDIT4.","authors":"Xin Wen, Ming Ji, Kuan Cao, Zhiyi Liu, Renhao Wang, Xingchao Song","doi":"10.1615/CritRevImmunol.2025060826","DOIUrl":"10.1615/CritRevImmunol.2025060826","url":null,"abstract":"<p><p>DNA Damage-Inducible Transcript 4 (DDIT4), a conserved stress-responsive protein with dual nuclear and cytoplasmic localization, has recently emerged as a critical regulator in multiple cancer types. However, its functional role and molecular mechanisms in hepatocellular carcinoma (HCC) remain poorly understood. In this study, we systematically investigated DDIT4's biological significance through comprehensive in vitro analyses. Clinical specimen analysis revealed significant downregulation of DDIT4 protein in HCC tumor tissues compared to adjacent non-tumor controls. Functional studies demonstrated that DDIT4 knockdown markedly enhanced HCC cell proliferation, whereas its overexpression exerted potent anti-proliferative effects. Mechanistically, our in vitro experiments revealed two key regulatory pathways: (1) DDIT4 overexpression suppressed AKT/mTOR signaling activation, and (2) DDIT4 underwent ubiquitin-mediated proteasomal degradation via specific interaction with the E3 ligase Seven in Absentia Homologue 2 (SIAH2). These findings establish DDIT4 as a tumor-suppressive protein in HCC pathogenesis, whose oncogenic downregulation is mediated through SIAH2-dependent ubiquitination. The resultant decrease in DDIT4 protein levels creates a permissive microenvironment for tumor growth by releasing AKT/mTOR pathway inhibition. Our results nominate DDIT4 as a promising therapeutic target for HCC intervention. Further preclinical and clinical investigations are warranted to validate DDIT4's translational potential and explore targeted strategies to stabilize its tumor-suppressive functions.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 1","pages":"17-26"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of an Immunogenic Cell Death-Related Long Non-Coding RNA Signature for Predicting Prognosis in Osteosarcoma.","authors":"Huihuang Luo","doi":"10.1615/CritRevImmunol.2025061145","DOIUrl":"10.1615/CritRevImmunol.2025061145","url":null,"abstract":"<p><p>Immunogenic cell death (ICD), a recently identified form of cell death capable of stimulating the immune system, holds significant potential for cancer therapy. While long non-coding RNAs (lncRNAs) regulate diverse cellular processes, the role and prognostic value of ICD-related lncRNAs (ICDRLs) in osteosarcoma (OS) remain unclear. This study aimed to establish an ICDRL-based prognostic signature for OS. Utilizing gene expression profiles and clinical data from TARGET and GTEx databases, along with published ICD-related genes (ICDRGs), we identified ICDRLs via co-expression analysis, differential expression screening, univariate Cox regression, and LASSO regression. A novel prognostic signature comprising three ICDRLs (ELFN1-AS1, LINC01094, SATB2-AS1) was constructed. The signature demonstrated significant prognostic predictive power, confirmed by receiver operating characteristic curve analysis, and functioned as an independent prognostic factor. Moreover, the signature reflects the tumor immune microenvironment and predicts distinct chemotherapy responses, guiding OS treatment strategies.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 1","pages":"45-57"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146230510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Supercharged NK Cells: A Novel NK Cell-Based Immunotherapy to Target Poorly Differentiated and Well-Differentiated Uterine Cancers.","authors":"Edward Sher, Sara-Huerta Yepez, Po-Chun Chen, Anahid Jewett, Kawaljit Kaur","doi":"10.1615/CritRevImmunol.2025060654","DOIUrl":"https://doi.org/10.1615/CritRevImmunol.2025060654","url":null,"abstract":"<p><p>This study delves into effective therapeutic strategies for endometrial cancer, focusing on the distinct functions of primary NK cells and supercharged NK (sNK) cells in targeting endometrial tumors. The research utilized AN3CA and HEC1B tumors to highlight the differences in efficacy between the two cell types. Notably, sNK cells exhibited the ability to target both stem-like AN3CA and well-differentiated HEC-1B tumors, while primary NK cells targeted the stem-like tumors exclusively. To demonstrate the in vivo effectiveness of sNK cells, AN3CA tumors were implanted in the uterus of humanized-BLT (hu-BLT) mice, followed by sNK cell therapy. The results showed that a single infusion of sNK cells significantly reduced tumor burden and restored immune cell function in the hu-BLT mice. This outcome underscores the potential of sNK therapy in eliminating stem-like, poorly differentiated, and well-differentiated tumors, while also enhancing the function of endogenous NK cells to better manage remaining tumors in patients. The findings of this study suggest that innovative treatments like sNK cell therapy represent the future of uterine cancer treatment, offering new avenues for effectively addressing the complexity of this disease.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 4","pages":"25-36"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Type I Interferons: Exploring Pathogenesis and Therapeutic Strategies in Autoimmune Diseases.","authors":"Sarvin Jabbari, Reza Safaralizadeh, Elmira Aboutalebi Vand Beilankouhi, Mohammad Valilo, Mohammadali Hosseinpourfeizi, Behzad Baradaran, Amir Khodavirdipour, Nima Hemmat","doi":"10.1615/CritRevImmunol.2026062673","DOIUrl":"10.1615/CritRevImmunol.2026062673","url":null,"abstract":"<p><p>Type I interferons (IFN-I) exert a significant influence on the immune system. Produced by certain immune cells, they affect other immune cells and mediate diverse effects, including antiviral activity, inhibition of tumor growth, and suppression of cell proliferation. IFN-I is also implicated in the development and persistence of autoimmune disorders. Research has shown that abnormal IFN-I levels and IFN-I-regulated gene expression in the blood or tissues of individuals with autoimmune diseases are associated with disease onset, clinical manifestations, and severity. Monogenic conditions known as Type I interferonopathies-caused by mutations affecting the IFN-I signaling pathway-share clinical features with systemic lupus erythematosus (SLE). Both preclinical models and clinical trials targeting the IFN-I signaling pathway have yielded promising results for the treatment of autoimmune diseases. This review provides an overview of the interplay between epigenetics, various types of RNAs, transcription factors, and IFN-I. It discusses epigenetic modifications and transcription factor dysregulation, offering insights into disease mechanisms and potential future therapeutic advancements.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 2","pages":"77-95"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148146078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC2A1-Dependent Ketone Metabolism Regulates Tumor Progression and Immunotherapy Efficacy in Lung Adenocarcinoma.","authors":"Xing Feng, Li Gao, Yonggang Xue, Yanbing Zhang, Hongyou Cao, Tianchang Wange","doi":"10.1615/CritRevImmunol.2026062879","DOIUrl":"10.1615/CritRevImmunol.2026062879","url":null,"abstract":"<p><p>The aim of this study is to identify and validate ketogenesis-immune cross-talk genes with prognostic significance in LUAD patients. Bulk RNA-seq data of LUAD were obtained from TCGA and GEO databases to analyze differentially expressed genes (DEGs), which were intersected with ketogenesis-related gene sets from MSigDB. DEGs associated with anti-PD-1 therapy sensitivity were further identified. Univariate and multivariate Cox regression analyses were performed to determine independent prognostic genes. Molecular subtypes and an 8-gene ketogenesis-immune prognostic signature were constructed and validated. Single-cell RNA-seq data were used to map cell-type-specific expression of prognostic genes. Functional effects of SLC2A1, a key metabolic regulator, were evaluated in A549 cells using overexpression/knockdown approaches combined with β-hydroxybutyrate (BHB) treatment. A total of 135 ketogenesis-immune cross-talk genes were identified. Consensus clustering defined two LUAD subtypes with distinct prognosis and immune landscapes. Single-cell analysis revealed SLC2A1 enrichment in epithelial tumor cells. Functional assays showed that SLC2A1 overexpression enhanced proliferation, migration, glycolysis, and ATP production, whereas knockdown suppressed these processes; BHB partially rescued energy deficits in SLC2A1-deficient cells. Mechanistically, SLC2A1 regulated ketone-body utilization and AMPK/mTOR signaling, linking metabolic reprogramming with tumor growth and immune modulation. SLC2A1 is a critical regulator of ketone-body metabolism in LUAD and serves as a potential prognostic factor.</p>","PeriodicalId":521264,"journal":{"name":"Critical reviews in immunology","volume":"46 2","pages":"59-76"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148146080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}