{"title":"Interleukin 16 in lupus nephritis - a role for Th1 and CD8+ T cell migration.","authors":"Kittikorn Wangriatisak, Francesca Faustini, Masa Filipovic, Heidi Wähämaa, Vivianne Malmström, Iva Gunnarsson, Vilija Oke","doi":"10.1093/cei/uxaf068","DOIUrl":"https://doi.org/10.1093/cei/uxaf068","url":null,"abstract":"<p><strong>Introduction: </strong>Dysregulation of interleukin (IL) 16 has been implicated in SLE, yet its cellular source and role in disease pathogenesis remain unclear.</p><p><strong>Method: </strong>We analysed circulating IL16+ immune cells from forty SLE patients, including 32 with active disease (SLEDAI-2K ≥ 4) using spectral flow cytometry. Plasma (pIL16) and urine IL16 (uIL16) levels were measured, and correlations with clinical variables were assessed. IL16 effects on T cell migration were studied in vitro.</p><p><strong>Results: </strong>Active SLE patients showed broadly reduced proportions of cells expressing IL16, including CD4+T, CD8+T, B and NK cells. This reduction was prominent in several cell subsets including Th1-like cells and plasmablasts. Further sub-analyses of lupus nephritis (LN) versus non-LN, demonstrated significantly reduced IL16 expression e.g. in Th1-like and double negative B cell subsets in LN. In parallel, SLE patients displayed increased pIL16 levels, and LN patients showed increased uIL16 which associated positively with disease activity SLEDAI-2K index and negatively with complement C4 levels and IL16+CD4+T cell counts. In vitro, IL16 induced CXCR4 and CCR5 mediated migration of Th1-cells and attracted CD8+T cells via CXCR4, which was partially inhibited by IL16 blockade.</p><p><strong>Conclusion: </strong>We demonstrate reduced intracellular IL16 expression in SLE lymphocytes, with low IL16+CD4+T cell proportions in LN correlating with increased uIL16. Extracellular IL16 may drive Th1 and CD8+T cell infiltration, contributing to organ inflammation. IL16 blockade reduced T cell migration, highlighting its potential as therapeutic target.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Post-transarterial chemoembolization hypoxia-induced HIF-1α/WNT/β-catenin signaling promotes hepatocellular carcinoma progression via programmed death ligand 1 upregulation.","authors":"Jiayan Ni, Shanshan Liu, Xue Han, Gefan Guo, Xiong Zhou, Hongliang Sun, Jinhua Huang, Linfeng Xu","doi":"10.1093/cei/uxaf067","DOIUrl":"https://doi.org/10.1093/cei/uxaf067","url":null,"abstract":"<p><strong>Introduction: </strong>Post-transarterial chemoembolization (TACE) hypoxia plays a crucial role in hepatocellular carcinoma (HCC) progression. However, the effects of post-TACE hypoxia on HCC progression are not fully understood yet. This study aims to elucidate the effects of post-TACE hypoxia-induced hypoxia-inducible factor-1α (HIF-1α)/WNT/β-catenin signaling on HCC progression.</p><p><strong>Methods: </strong>In this study, serum concentrations of soluble programmed death ligand 1 (sPD-L1) and HIF-1α in HCC patients who underwent TACE were measured using enzyme-linked immunosorbent assay (ELISA). In vitro, WNT/β-catenin pathway activation was assessed by TOP/FOP luciferase activity, while HIF-1α-siRNA transfection was used to observe the interaction between HIF-1α and WNT/β-catenin. In vivo, mouse xenograft tumor models were used to examine the effects of programmed death ligand 1 (PD-L1) on HCC progression and to verify the correlations among HIF-1α, WNT/β-catenin, and PD-L1. The mechanisms underlying hypoxia-induced PD-L1 overexpression were studied using chromatin immunoprecipitation (ChIP).</p><p><strong>Results: </strong>Median post-TACE serum sPD-L1 and HIF-1α concentrations in HCC patients were significantly higher compared to pre-TACE levels, with a significant correlation observed between sPD-L1 and HIF-1α. In vitro studies demonstrated that hypoxia promoted WNT/β-catenin activation and PD-L1 expression. HIF-1α silencing significantly inhibited WNT/β-catenin activation. In vivo, hypoxia-induced PD-L1 overexpression significantly promoted HCC progression. WNT/β-catenin activation increased PD-L1 promoter luciferase activity, and ChIP confirmed that LEF1 bound to the PD-L1 promoter in hypoxic hepatoma cells.</p><p><strong>Conclusion: </strong>Post-TACE hypoxia-induced activation of HIF-1α/WNT/β-catenin signaling promotes HCC progression by upregulating PD-L1 expression.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Children with Recurrent Infections: Perspective of Immunoglobulin G Subclasses Deficiency and Impaired Specific Antibody Responses.","authors":"Jalilah Jamaluddin, Siti Mardhiana Binti Mohamad, Intan Hakimah Ismail","doi":"10.1093/cei/uxaf066","DOIUrl":"https://doi.org/10.1093/cei/uxaf066","url":null,"abstract":"<p><p>Children with recurrent infections present a diagnostic challenge due to the wide overlap between normal childhood infections and primary immunodeficiency diseases (PIDs). Predominantly antibody deficiencies (PADs) are the most common category of PID in this population. While many PAD cases are identified through markedly low immunoglobulins levels or reduced B cell counts, some demonstrate subtler forms such as IgG subclass deficiency (IGGSD) or specific antibody deficiency (SAD), which may present similar clinical symptoms but normal standard laboratory parameters. Diagnosing these conditions in children is particularly challenging due to the overlap with physiological immune immaturity and the high incidence of infections in early childhood. Clinicians must carefully distinguish between benign infection patterns and true immunodeficiencies to avoid missed diagnoses and unnecessary investigations. This review summarizes key findings on IGGSD and SAD, highlights their clinical relevance in paediatric practice, and evaluates current challenges in diagnosis and classification. We also discuss the overlap between these conditions and propose a structured approach to improve diagnostic consistency. Addressing these knowledge gaps is essential to optimize care for children with recurrent infections and suspected antibody deficiencies.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Danai Bagkou Dimakou, Nicholas E Peters, Siobhan O Burns, Alex G Richter, Adrian M Shields
{"title":"Serum sBCMA in primary and secondary antibody deficiency.","authors":"Danai Bagkou Dimakou, Nicholas E Peters, Siobhan O Burns, Alex G Richter, Adrian M Shields","doi":"10.1093/cei/uxaf065","DOIUrl":"https://doi.org/10.1093/cei/uxaf065","url":null,"abstract":"<p><strong>Background: </strong>B-cell maturation antigen (BCMA) is a B cell surface receptor that regulates activation, proliferation and survival. BCMA can be cleaved from the cell surface, producing soluble BCMA (sBCMA), which has been studied as a disease biomarker in systemic lupus erythematosus, multiple sclerosis and multiple myeloma. Reduced sBCMA concentrations have been associated with the severity of different primary antibody deficiencies.</p><p><strong>Aims and methods: </strong>We explored the relationship between sBCMA concentrations, humoral immune responses to SARS-CoV-2 vaccination and disease complications in 107 individuals with primary and secondary antibody deficiency enrolled in the COVID-19 in Antibody Deficiency (COV-AD) study.</p><p><strong>Results: </strong>Serum sBCMA concentrations were significantly reduced in primary antibody deficiencies compared to healthy controls and asymptomatic selective IgA deficiency. Individuals with X- linked agammaglobulinemia and common variable immunodeficiency (CVID) demonstrated the lowest serum concentrations of sBCMA. sBCMA concentrations in secondary antibody deficiency were highly variable. Amongst individuals with CVID, peripheral blood CD19 count, but not sBCMA concentrations discriminated SARS-CoV-2 vaccine responders. sBCMA was significantly lower in individuals with CVID and bronchiectasis and outperformed serum IgA and IgM concentrations in discriminating this subgroup. sBCMA was not associated with any other complication of CVID.</p><p><strong>Conclusion: </strong>Our data highlights the potential of sBCMA as biomarker to support the assessment of antibody deficiency. In primary antibody deficiencies, it may contribute to the risk stratification of disease severity and identify those at risk of bronchiectasis. In secondary antibody deficiency, it may identify subgroups that would benefit from intensive monitoring and therapy.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytokines dynamics and biological sex differences in SARS-CoV-2 infected people in Cameroon.","authors":"Hillary Tene, Romuald Ngamaleu, Romeo Djounda, Rachel Minomo, Sabine Ngale, Micheal Besong, Honore Awanakam, Krystelle Nganou Makamdop, Rene Essomba, Jude Bigoga, Daniel C Douek, Livo Esemu","doi":"10.1093/cei/uxaf063","DOIUrl":"https://doi.org/10.1093/cei/uxaf063","url":null,"abstract":"<p><strong>Introduction: </strong>Cytokine storm can result from uncontrolled proinflammatory cytokines released in SARS-CoV-2 infection that cause damage to several organs. Il-6 is one of the major mediators of cytokine storm. IFN-α2 has been reported to have anti-viral potential and the pre-infection levels of proinflammatory cytokines have been suggested to drive the fate of the disease. There is a paucity of information on how anti-viral cytokines at the onset of infection affect the disease progression. This study aims to profile IL-2, IL-6, IL-10, and IFN-α2 expression levels for 44 days post-diagnosis and their effects on recovery.</p><p><strong>Methods: </strong>Peripheral venous blood was collected from 38 SARS-CoV-2 infected participants who came for diagnosis at the Center for Research on Emerging and Reemerging Diseases. IL-2, IL-6, IL-10, and IFN-α2 levels were measured using a Luminex panel.</p><p><strong>Results: </strong>Males had higher SARS-CoV-2 viral load than females, although the difference was not statistically significant (p=0.08). Age-related variation was also observed, with individuals aged 40-60 showing significantly higher viral load than those over 60 (p=0.045). Cytokines analysis revealed that males had significantly higher levels of IFNα-2, IL-2, and IL-6 (p=0.0031, p=0.009, and p=0.022 respectively) than females upon diagnosis, with cytokines levels decreasing over time in males but increasing in females. Cytokine levels trended higher in symptomatic individuals, although differences were not significant.</p><p><strong>Conclusion: </strong>These findings highlight the influence of sex, clinical status, and viral load on cytokine dynamics in COVID-19, with potential implications for understanding disease severity and immune response.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Un-personalised medicine: the challenges of vaccines as a single medicine for a whole population.","authors":"John S Tregoning, Vanessa Sancho-Shimizu","doi":"10.1093/cei/uxaf062","DOIUrl":"https://doi.org/10.1093/cei/uxaf062","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adekunle A Adeniran, Gavin Giovannoni, David Baker, Louisa K James
{"title":"Epstein-Barr Virus and spontaneous lymphoblastoid cell lines: establishment, molecular characteristics, immune modulation, and therapeutic insight.","authors":"Adekunle A Adeniran, Gavin Giovannoni, David Baker, Louisa K James","doi":"10.1093/cei/uxaf061","DOIUrl":"https://doi.org/10.1093/cei/uxaf061","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is a ubiquitous herpesvirus with well-established oncogenic potential, contributing to various malignancies and immune-mediated diseases. Its capacity to infect and immortalize B-cells forms the basis for the generation of lymphoblastoid cell lines (LCLs), which serve as vital models in immunology, virology, and translational research. While conventional LCLs are produced by exogenous EBV infection of peripheral blood mononuclear cells, spontaneous lymphoblastoid cell lines (S-LCLs) can emerge without deliberate viral inoculation, particularly in EBV-seropositive individuals. This review highlights multiple methodologies used to establish S-LCLs, including the use of cyclosporin A, CpG DNA, checkpoint kinase inhibitors, and cytokine modulation, and presents findings from diverse clinical contexts such as autoimmune diseases, post-transplant lymphoproliferative disorders, and cancer. We discuss the biological mechanisms underpinning EBV latency and reactivation, emphasizing the viral transcriptional programs that drive B-cell transformation and persistence. Additionally, we explore how cytokines, particularly IL-10, support S-LCL survival, and how sodium butyrate and antiviral agents like acyclovir can influence EBV reactivation and replication. The review also considers the diagnostic and therapeutic relevance of LCLs, including their potential as antigen-presenting cells, vaccine platforms, and models for cellular immunotherapies such as CAR T-cells and virus-specific cytotoxic T lymphocytes. By evaluating the generation, molecular features, and immunological significance of S-LCLs, this review underscores their value in modelling EBV-driven disease and advancing novel therapeutic strategies.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katie Townsend, Shichina Kannambath, Grant Hayman, Rainer Doffinger, Lourdes Ceron-Gutierrez, Soraya Ebrahimi, Vlada Pavlova, Philip Gothard, Michael Brown, Fariba Tahami, Dakshika Jayaratnam, Anna L Goodman, Derek Macallan, Thomas S Harrison, Magda Dziadzio, Jonathan Lambourne, Tanaraj Perinpanathan, Laurence John, Neil Stone, Tihana Bicanic, David M Lowe
{"title":"Immunophenotyping of apparently immunocompetent hosts with cryptococcosis reveals IL-17 deficiency as a unifying susceptibility factor.","authors":"Katie Townsend, Shichina Kannambath, Grant Hayman, Rainer Doffinger, Lourdes Ceron-Gutierrez, Soraya Ebrahimi, Vlada Pavlova, Philip Gothard, Michael Brown, Fariba Tahami, Dakshika Jayaratnam, Anna L Goodman, Derek Macallan, Thomas S Harrison, Magda Dziadzio, Jonathan Lambourne, Tanaraj Perinpanathan, Laurence John, Neil Stone, Tihana Bicanic, David M Lowe","doi":"10.1093/cei/uxaf053","DOIUrl":"https://doi.org/10.1093/cei/uxaf053","url":null,"abstract":"<p><strong>Introduction: </strong>We describe the immunophenotyping and genetic analysis of HIV-uninfected apparently immunocompetent adults presenting with disseminated cryptococcosis. Cryptococci are environmentally ubiquitous fungi that may cause disseminated infection including meningitis. Cryptococcosis occurs predominantly in immunocompromised hosts and most commonly in the context of human immunodeficiency virus (HIV) infection. In apparently immunocompetent patients, cryptococcal disease is rare, often diagnosed later and associated with higher mortality. The immunologic work-up and management of this patient group is challenging and poorly studied.</p><p><strong>Methods: </strong>Between 2015-2021, eight apparently immunocompetent adults at the time of diagnosis with cryptococcosis underwent extensive diagnostic immunological work-up including T-/B-cell subsets, immunoglobulins, T-cell proliferation and phenotyping, serum-specific antibody responses, mannose binding lectin, measurement of selected cytokines, anti-cytokine autoantibodies and targeted genetic next-generation sequencing.</p><p><strong>Results: </strong>The production of interleukin (IL)-17 following phytohaemagglutinin (PHA) stimulation was significantly reduced in all eight patients with cryptococcosis compared to healthy controls (median IL-17 concentration in whole blood stimulation assay 88.1pg/mL in patients; 452.1pg/mL in controls, p=0.0047). In 5/5 patients tested, the percentage of CD4+ T-cells positive for IL-17, including memory CD4+CD45RO+ IL-17+ T-cells, after stimulation with staphylococcal enterotoxin B (SEB) was significantly reduced (<=0.4% cells). Reduced IgM+ memory B-cells were noted in 4/5 tested. 4/8 patients were found to have CD4 lymphopaenia. One patient with Cryptococcus gattii infection had autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). No underlying genetic causes were identified.</p><p><strong>Conclusion: </strong>Patients had several immunological risk factors, but reduced IL-17 production was a striking feature across the cohort - a phenotype that may facilitate tailored immunotherapeutic approaches.Graphical Abstract.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ke-Ming Ning, Wen-Bo Xu, Yi-Han Wang, Lei Lei, Wang-Si-Jiao Shen, Zhao-Ying Liu
{"title":"The Roles of GABA and NMDA Receptors in Viral Infections: Based on current literature.","authors":"Ke-Ming Ning, Wen-Bo Xu, Yi-Han Wang, Lei Lei, Wang-Si-Jiao Shen, Zhao-Ying Liu","doi":"10.1093/cei/uxaf052","DOIUrl":"https://doi.org/10.1093/cei/uxaf052","url":null,"abstract":"<p><p>Gamma-aminobutyric acid receptors (GABARs) primarily function by suppressing inflammatory responses, modulating neuronal excitability, and maintaining intracellular homeostasis, whereas N-methyl-D-aspartate receptors (NMDARs) play a key role in mediating pathological processes through the regulation of excitatory neurotransmission and immune responses. Viral infections have the capacity to modify the expression and functionality of these receptors, either directly or indirectly, thereby contributing to dysregulation within the neurological and immune systems and triggering a range of disease states. This review offers a comprehensive analysis of the mechanisms through which various viral infections interact with GABARs and NMDARs, emphasizing the possible intricate roles these receptors play in viral pathogenesis. Additionally, it underscores their potential as therapeutic targets for antiviral interventions, particularly in addressing immune dysregulation and neurological disorders.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiameng Gao, Zhiyuan Zhang, Yang Jin, Nan Zhang, Yu Fu, Xuemei Jiang, Xingan Wang, Zongmei Wen
{"title":"Primary graft dysfunction after Lung transplantation: unveiling the role of innate immunity.","authors":"Jiameng Gao, Zhiyuan Zhang, Yang Jin, Nan Zhang, Yu Fu, Xuemei Jiang, Xingan Wang, Zongmei Wen","doi":"10.1093/cei/uxaf046","DOIUrl":"https://doi.org/10.1093/cei/uxaf046","url":null,"abstract":"<p><p>Primary graft dysfunction (PGD) represents a clinical acute lung injury syndrome occurring within 72 hours after lung transplantation, remaining the main cause of early mortality after lung transplantation. However, very few effective and specific therapies are available, except for supportive treatment. Broad cellular and molecular mechanisms contribute to PGD, yet the precise mechanism remains poorly understood. The major underlying pathophysiology of PGD is ischemia-reperfusion injury (IRI), which inevitably occurs during lung transplantation. Ischemia and subsequent reperfusion of donor lungs commonly trigger cellular and molecular dysfunction, causing disorders of metabolism and ionic homeostasis, release of reactive oxygen species (ROS), dysfunction of mitochondria, secretion of inflammatory cytokines, and activation of innate immunity. These events induce both programmed and non-programmed cell death, leading to vascular and alveolar epithelial damage, pulmonary edema, and impaired gas exchange. Innate immune activation during lung ischemia-reperfusion unfolds in two distinct phases, with the early phase primarily driven by donor-derived immune cells and the late phase mainly driven by recipient-derived immune cells. This review systematically summarizes the pathophysiology of PGD from the perspective of cellular and molecular aspects, especially emphasizing the process of programmed cell death and dynamic innate immune cell migration, which might potentially provide novel insights into the prevention and targeted therapy for IRI and PGD after lung transplantation.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}