Immunologic Research最新文献

{"title":"The invisible agitators: exploring the viral interplay in psoriatic immune dysregulation.","authors":"Snehasis Nayak, Budhera Nithika Reddy, Sri Vaibhav Kintali","doi":"10.1007/s12026-025-09692-9","DOIUrl":"https://doi.org/10.1007/s12026-025-09692-9","url":null,"abstract":"<p><p>This review explores the complex interplay between viral infections and psoriasis. It emphasizes how viruses like HIV, hepatitis, herpes, human papillomavirus, and SARS-CoV-2 can provoke and worsen psoriatic inflammation by disturbing immune balance. A key focus of the discussion is the IL-23/Th-17 pathway, which drives the production of proinflammatory cytokines that promote keratinocyte overgrowth and perpetuate chronic skin inflammation. Our article further investigates how disrupted intracellular pathways-such as those involving PI3K, Wnt signaling, and caveolin-affect the severity of the disease. This review supports the idea that viral infections can not only trigger psoriatic lesions but may also increase the risk of additional viral reactivation, thereby complicating the clinical picture of psoriasis. This thorough evaluation highlights the necessity for focused research to create innovative therapeutic strategies aimed at these viral triggers.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"140"},"PeriodicalIF":3.1,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225125","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":"Trained Immunity in sepsis: Exploring the molecular link to long-term cardiometabolic disorders.","authors":"Rijhul Lahariya, Gargee Anand, Bandana Kumari","doi":"10.1007/s12026-025-09698-3","DOIUrl":"https://doi.org/10.1007/s12026-025-09698-3","url":null,"abstract":"<p><p>Sepsis, a life-threatening systemic infection, has long been recognized for its immediate risks, but its long-term consequences on health are increasingly evident, particularly in predisposing survivors to chronic cardiometabolic disorders (CMDs) such as atherosclerosis, insulin resistance, and dyslipidemia. Central to this process is trained immunity, where innate immune cells like monocytes, macrophages, and neutrophils undergo long-lasting epigenetic reprogramming after sepsis. This reprogramming, sustained by molecular pathways such as NF-κB, mTOR, and altered lipid metabolism, drives chronic inflammation, oxidative stress, and metabolic dysfunction, contributing to long-term cardiovascular diseases (CVDs) and metabolic disorders post-sepsis. This review explores the key mechanisms through which trained immunity bridges sepsis and CMDs, particularly focusing on epigenetic modifications such as histone acetylation, DNA methylation, and mitochondrial alterations. We discuss how trained immunity enhances immune cell activation, leading to persistent low-grade inflammation, lipid dysregulation, and impaired insulin sensitivity, all of which predispose sepsis survivors to CVDs. Additionally, we highlight potential therapeutic approaches targeting trained immunity, including statins, which reduce inflammation and immune reprogramming; metformin, which restores metabolic balance by activating AMPK and reducing oxidative stress; dimethyl fumarate (DMF), a potent Nrf2 activator that counteracts inflammation; and probiotics, which help restore gut microbiota balance and limit endotoxin-driven inflammation. These therapies offer promising strategies to mitigate long-term metabolic dysfunction and reduce the incidence of CMDs following sepsis. Understanding these mechanisms and developing targeted interventions may ultimately help prevent chronic cardiovascular and metabolic diseases in sepsis survivors and improve long-term outcomes.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"139"},"PeriodicalIF":3.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199160","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":"Sequence similarity-based candidate gene prioritization for Type 1 diabetes mellitus using moment of inertia tensor.","authors":"Eesam Vishnu, Nithya Chandramohan, P Manimaran","doi":"10.1007/s12026-025-09697-4","DOIUrl":"https://doi.org/10.1007/s12026-025-09697-4","url":null,"abstract":"<p><p>In this paper, the study focuses on Type 1 Diabetes Mellitus (T1D), a chronic condition that affects the insulin-producing cells of the pancreas, requiring individuals to depend on external insulin for survival. We introduce a novel method for analyzing protein sequences by treating them as rigid bodies with mass and moment of inertia to assess sequence similarity. This method transforms the protein sequences into vectors using the moment of inertia tensor, with similarity calculated using Euclidean distance. Using this technique, we identified 24 genes linked to T1D, showing significant similarities to known T1D-related genes and highlighting their potential importance in the disease. Further, we conduct functional enrichment analysis for better understanding, which is very helpful for investigating their roles in various biological processes and molecular functions. The Gene Ontology (GO)analysis is crucial for prioritizing the identified genes and providing insights into their contributions to T1D pathophysiology. To combine the concepts from physics with computational biology, our research not only increases the understanding of T1D disease but also introduces an innovative approach for gene discovery and functional analysis in autoimmune diseases.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"138"},"PeriodicalIF":3.1,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185816","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":"Piceatannol improves autoimmune hepatitis by inhibiting the immune activities of T cells and macrophages through binding with c-Jun.","authors":"Cong Xu, Chenqi Lu, Wu Wang, Zhimin Wang, Yang Qiu, Min Han, Jun Yang, Shanglin Li","doi":"10.1007/s12026-025-09689-4","DOIUrl":"https://doi.org/10.1007/s12026-025-09689-4","url":null,"abstract":"<p><p>Autoimmune hepatitis (AIH) is an immune-mediated liver disease that currently lacks viable drug treatment methods. This study is to explore the role of piceatannol (PIC) in ConA-induced AIH and the related mechanisms. A mouse model of AIH was established by injecting ConA (i.v.), and PIC was administered as an intervention. The protective effect of PIC was evaluated by the liver function, liver pathology, and serum levels of inflammatory factors. Subsequently, network pharmacology was used to predict the pathways and targets of PIC in the treatment of AIH, and the predicted results were validated using flow cytometry, molecular docking, surface plasmon resonance (SPR) and so on. Finally, the immunosuppressive effect of PIC was further validated in a mouse heart transplantation model. PIC can improve liver function decline and reduce pathological liver damage, as well as inhibit the increase of serum inflammatory factor levels in mice with AIH induced by ConA. The protective effect is achieved by suppressing the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts and inhibit acute rejection reactions. These results indicated that PIC can significantly improve ConA-induced AIH in mice by inhibiting the immune activity of T cells and macrophages through binding to c-Jun. PIC can also extend the survival of cardiac allografts in mice and inhibit acute rejection responses. The above results indicated that PIC may serve as a promising immunosuppressant and be effective for AIH.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"137"},"PeriodicalIF":3.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174943","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":"Engineering CAR-T cells for solid tumors: bispecific antigen targeting, tumor microenvironment modulation, and toxicity control.","authors":"Tanvi Premchandani, Mohammad Qutub, Amol Tatode, Milind Umekar, Jayshree Taksande, Ujban Md Hussain, Sameer R Khidkikar","doi":"10.1007/s12026-025-09687-6","DOIUrl":"https://doi.org/10.1007/s12026-025-09687-6","url":null,"abstract":"<p><p>Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematologic malignancies, yet its efficacy in solid tumors remains limited due to antigen heterogeneity, immunosuppressive tumor microenvironments, and therapy-associated toxicities. This review highlights advances across CAR-T generations, emphasizing co-stimulatory domains and cytokine-armed TRUCKs to enhance persistence and function. Viral (lentiviral, gamma-retroviral) and non-viral (CRISPR, transposons, mRNA electroporation) delivery systems are compared for efficiency, safety, and scalability, with CRISPR enabling multiplex edits for improved specificity. Dual-targeting CARs counter antigen heterogeneity, while hypoxia-inducible and SynNotch CARs restrict activity to tumor sites. Chemokine receptor engineering enhances infiltration, and armored CARs secreting IL-12 or checkpoint inhibitors remodel the TME. Nanobody-based CAR-T cells further expand design versatility, offering improved stability, tumor penetration, and reduced immunogenicity compared with single-chain variable fragment constructs. Safety innovations include iCasp9 Suicide switches, dasatinib-controlled activation, and cytokine blockade. Clinical trials of bispecific CAR-Ts show promise, yet challenges Like manufacturing complexity and off-target effects persist. Integrating AI-driven design and Personalized neoantigen targeting may unlock CAR-T 2.0 for solid tumors, pending scalable production and regulatory harmonization.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"135"},"PeriodicalIF":3.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091695","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":"Associative study of human herpesvirus 8 and Kaposi's sarcoma: Mapping viral oncogenic properties and the clinical scenario in oncological patients.","authors":"João Vitor Geisteira Oliveira da Silva, Jessica Manya Bittencourt Dias Vieira, Eidy de Oliveira Santos","doi":"10.1007/s12026-025-09684-9","DOIUrl":"https://doi.org/10.1007/s12026-025-09684-9","url":null,"abstract":"<p><p>Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), is the etiological agent of Kaposi's Sarcoma (KS) and other lymphoproliferative disorders. Over three decades after its discovery, many aspects of its biology, latency, immune evasion, and oncogenic mechanisms remain poorly understood. This review provides an integrative and up-to-date analysis of KSHV, from its molecular architecture and gene regulation to its complex host interactions and transmission dynamics. We highlight key viral proteins-LANA, RTA, vFLIP, vCyc, kaposins, and viral miRNAs-that orchestrate latency maintenance, lytic reactivation, immune modulation, and tumor development. The review maps how KSHV establishes persistent infection, exploits host signaling pathways, and induces hallmarks of cancer, such as angiogenesis and uncontrolled proliferation. We also discuss glycoprotein-receptor interactions involved in viral entry and the structural mechanisms facilitating KSHV-cell fusion. Clinically, we present updated epidemiological data and analyze the diversity of KS forms-classic, endemic, iatrogenic, epidemic, and anaplastic-highlighting regional disparities, diagnostic challenges, and treatment gaps. The article emphasizes the virus's role in aggressive neoplasms in immunocompromised individuals and underscores the lack of antiviral strategies specifically targeting KSHV. By combining molecular virology, oncogenesis, immunology, and epidemiology, this review advances the current understanding of KSHV and reinforces the urgent need for effective diagnostic tools, preventive strategies, and targeted therapies. Our findings contribute to bridging knowledge gaps and promoting translational approaches to mitigate the global impact of KSHV-related diseases.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"136"},"PeriodicalIF":3.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091705","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":"The double-edged sword of PI3Kδ pathway-related immune dysregulation: insights from two case reports.","authors":"Marta Dafne Cabanero-Navalon, Victor Garcia-Bustos, Santos Ibanez-Barcelo, Héctor Balastegui-Martin, Javier Grimaldos-Lodares, Pedro Moral-Moral","doi":"10.1007/s12026-025-09691-w","DOIUrl":"10.1007/s12026-025-09691-w","url":null,"abstract":"<p><p>Phosphoinositide 3-kinases (PI3Ks), particularly the PI3Kδ pathway, play a crucial role in regulating immune functions. Alterations in this pathway, either as hyperactivation, such as in activated PI3Kδ syndrome (APDS), or rarely described hypoactivation, profoundly influence immune function and are linked to a spectrum of immunodeficiencies and autoimmune conditions. This report describes two cases of late-onset immunodeficiencies associated with PI3Kδ pathway dysregulation, each presenting with unique mutations and clinical manifestations. The first case involves a heterozygous mutation in PI3KR1 (c.5A > T, p.Tyr2Phe) indicative of PI3Kδ hyperactivation, effectively managed with sirolimus. The second case is characterized by a homozygous mutation in PIK3CD (c.2608C > T, p.Arg870Ter), suggesting PI3Kδ hypoactivation, with clinical features including psoriatic arthritis and ulcerative colitis. These cases underscore the heterogeneous clinical features and the challenges in managing such rare genetic variants. These cases underscore the importance of considering primary immunodeficiency in individuals exhibiting signs of both infectious and non-infectious autoimmune or immune dysregulation complications. Prompt genetic screening and strategic therapeutic approaches are crucial for effectively managing these conditions and mitigating the risks associated with immunosuppressive treatments. These insights emphasize the need for a deeper understanding of genetic factors in immunodeficiencies to devise personalized treatment strategies that substantially improve patients' quality of life.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"132"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086020","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":"A rare autoinflammatory syndrome associated with a C2orf69 frameshift mutation: a case report.","authors":"Şeyma Türkmen, Murat Hakkı Yarar, İlkay Tosun, Hayrunnisa Bekis Bozkurt, Betül Sözeri","doi":"10.1007/s12026-025-09693-8","DOIUrl":"https://doi.org/10.1007/s12026-025-09693-8","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"134"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086069","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":"Monocyte plasticity and HLA-DR expression in patients with X-linked agammaglobulinemia.","authors":"Hasibe Artac, Ayca Ceylan, Ilknur Kulhas Celik, Figen Celebi Celik, Yasin Karali, Zeynep Meric, Demet Tekcan, Mehmet Geyik, Selcen Bozkurt, Saliha Esenboga, Zehra Şule Haskoloğlu, Esra Ozek Yucel, Nesrin Gulez, Neslihan Edeer Karaca, Sevgi Bilgic Eltan, Sukru Nail Guner, Cigdem Aydogmus, Mehmet Halil Celiksoy, Esra Karabiber, Ferah Genel, Esin Figen Doğu, Elif Karakoc-Aydiner, Deniz Cagdas, Guzide Aksu, Ayca Kiykim, Sara Sebnem Kilic, Sevgi Keleş, Kamile Aydan Ikinciogullari, İsmail Reisli","doi":"10.1007/s12026-025-09690-x","DOIUrl":"https://doi.org/10.1007/s12026-025-09690-x","url":null,"abstract":"<p><p>Bruton's tyrosine kinase (BTK) is expressed by innate immune cells, and it has been suggested that a lack of BTK may affect monocytes, impacting infection susceptibility and inflammatory response in patients with X-linked agammaglobulinemia (XLA). This study aimed to explore the role of monocyte subsets and monocyte human leucocyte antigen DR (mHLA-DR) expression in patients with XLA. Fifty-nine patients diagnosed with XLA and 37 age-matched healthy subjects were enrolled, and their demographic and clinical features were recorded. Three monocyte subsets were identified-classical (CL) (CD14⁺⁺CD16^-), intermediate (INT) (CD14⁺⁺CD16⁺), and non-classical (NC) (CD14^lowCD16⁺⁺)-and their mHLA-DR expressions (mean fluorescence intensity, MFI) were determined by flow cytometry. We evaluated monocyte plasticity as the classical/intermediate monocyte (CMIM) ratio. Patients with XLA comprised 38 children (mean age, 10.46 ± 4.81 years) and 21 adults (25.09 ± 6.18 years). Compared to the control group, patients had decreased classical (p = .012) but increased intermediate and non-classical monocytes (p < .001 and p = .048, respectively). They also presented with increased mHLA-DR expression of total monocytes and their subsets compared to the healthy subjects (p < .05). There were 17 patients with bronchiectasis (28.8% of total, three children and 14 adults), and they had decreased mHLA-DR of non-classical monocytes and a low CMIM ratio compared with non-bronchiectasis XLA patients (p < .001). The study findings may indicate that a defect in adaptive immune mechanisms leads to compensatory changes in the innate immune system. Monocyte HLA-DR expression and CMIM ratio can be used as potential biomarkers to predict chronic complications, including bronchiectasis in patients with XLA.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"133"},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085999","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":"Optimizing antiphospholipid antibody testing: a real-world analysis of appropriateness and resource utilization.","authors":"Silvia Grazietta Foddai, Maria Infantino, Mariangela Manfredi, Francesca Pavia, Maurizio Benucci, Francesca Li Gobbi, Massimo Radin, Irene Cecchi, Alice Barinotti, Savino Sciascia","doi":"10.1007/s12026-025-09682-x","DOIUrl":"10.1007/s12026-025-09682-x","url":null,"abstract":"<p><p>Efficient utilization of healthcare resources, including laboratory testing, is crucial for environmental sustainability and cost-effectiveness. The diagnosis of APS requires the presence of at least one clinical event (either an objectively confirmed thrombotic event and/or pregnancy complication) and detection of one or more aPL (lupus anticoagulant [LA], IgG/IgM anticardiolipin [aCL], and/or IgG/IgM anti-β2 glycoprotein-1 [aβ2GPI]). However, inappropriate requests for aPL tests contribute to unnecessary healthcare expenses and environmental impact. This study evaluates the appropriateness of aPL testing in a clinical setting. A retrospective analysis was conducted on 642 patients attending the San Giovanni Di Dio Hospital, Florence (11/2023-02/2024). Diagnostic suspicion underlying aPL test requests were classified as appropriate, inappropriate, or unevaluable using a scoring system based on clinical recommendations. Appropriateness assessment was performed independently by two researchers and reconciled with a third expert. Patient demographics, test results, and the specialty of the physicians ordering aPL were recorded and analyzed. Of the 642 queries, 36% were deemed appropriate, 42% inappropriate, and 22% unevaluable. Family physicians accounted for 53% of all test requests but exhibited the highest rate of inappropriate requests (44%). Rheumatologists, internal medicine physicians, and gynecologists demonstrated better adherence to recommendations (with 34%, 30%, and 18% of inappropriate requests, respectively). Only 4.9% of patients underwent comprehensive aPL testing per international standards (Sidney criteria). Among the 115 aPL-positive cases, multiple antibody positivity was more common in appropriate test requests. Inappropriate requests often stemmed from conditions without established links to APS, such as alopecia, hypercholesterolemia, and dysmenorrhea. A considerable proportion of aPL testing in routine practice lacks clinical justification, reflecting variability in guideline adherence across specialties. Inappropriate testing increases healthcare costs, specialist referrals, and environmental burdens. Improved education, adherence to diagnostic recommendations, and sustainable practices are critical to optimizing APS testing and resource utilization.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"130"},"PeriodicalIF":3.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075085","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}