Frontiers in Immunology最新文献

{"title":"Progress in research on gut microbiota regulation of tumorigenesis, progression, and therapeutic response via inflammatory cytokines.","authors":"Yan Liu, Dan Zang, Jun Chen","doi":"10.3389/fimmu.2026.1922678","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1922678","url":null,"abstract":"<p><p>The gut microbiota has emerged as an important regulator of tumour biology through dynamic interactions with host immune and inflammatory networks. A growing number of preclinical studies and observational clinical studies suggest that dysbiosis-associated changes in microbial composition and metabolite profiles can remodel inflammatory signalling pathways and are associated with tumour initiation, progression, metastasis, and therapeutic response. Microbial components and metabolites can activate pattern-recognition receptor-related pathways, including nuclear factor kappa B (NF-κB), in cell and animal models. These changes may promote a tumour-supportive chronic inflammatory milieu or, under specific ecological conditions, help shape an immune-activated microenvironment. Current evidence also suggests that the gut microbiota and inflammatory cytokines may influence treatment response. Preclinical models and some patient cohort studies indicate that dysregulated inflammatory responses are associated with reduced chemotherapy tolerance and a higher risk of immune-related adverse events (irAEs), whereas certain beneficial microbial signals are associated with enhanced CD8⁺ T-cell activation and improved efficacy of immune checkpoint inhibitors (ICIs). However, these associations vary across cancer types and study populations, and their causality and clinical generalizability still require further validation. In this Review, we summarize current evidence on how the gut microbiota and inflammatory cytokines jointly regulate tumour development and therapeutic outcomes. We also discuss therapeutic strategies that target microbial composition and inflammatory signalling, with emphasis on their translational potential in precision oncology.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1922678"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13697595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dried blood spot IP-10 as a biomarker of tuberculosis severity and treatment responses: results from a phase IIb trial of adjunctive acetylsalicylic acid and ibuprofen.","authors":"Iselin Høgbakk Edlund, Noelia Alonso-Rodriguez, Chiara Sopegno, Judith Farrés, Nino Gogichadze, Lilibeth Arias, Kaori L Fonseca, Kennedy Otwombe, Ziyaad Waja, Tumelo Moloantoa, Natasha Pillay, Thabiso Seiphetlo, Neil Martinson, Cristina Vilaplana, Anne Ma Dyrhol-Riise","doi":"10.3389/fimmu.2026.1924239","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1924239","url":null,"abstract":"<p><strong>Background: </strong>Host-directed therapies may improve tuberculosis (TB) outcomes by modulating immune responses and attenuating hyperinflammation, yet accessible biomarkers remain limited. We hypothesized that interferon-γ-inducible protein 10 (IP-10/CXCL10) measured in dried blood spot (DBS), a low-threshold and field-adapted sampling method, has potential as a biomarker for treatment response in pulmonary TB. Accordingly, we assessed IP-10 levels in patients receiving adjunctive acetylsalicylic acid (ASA) or ibuprofen (IBU) alongside TB standard therapy.</p><p><strong>Methods: </strong>IP-10 levels were quantified longitudinally in DBS from 120 pulmonary TB patients enrolled in the SMA-TB clinical trial (NCT04575519) at two sites in South Africa. Samples collected at baseline, week 2, week 8, and week 24 were analyzed by the enzyme-linked immunosorbent assay (ELISA). Associations with disease severity and treatment response were assessed, and the predictive value of IP-10 for microbiological, clinical, and radiological outcomes was evaluated.</p><p><strong>Results: </strong>IP-10 levels correlated with TB disease severity, with higher concentrations observed in patients with elevated clinical and radiological scores and positive sputum acid-fast-bacilli staining. This association was reflected in treatment response, as patients with good clinical outcomes exhibited an earlier decline in IP-10 (week 8, p=0.0005), whereas those with poor outcomes showed a delayed decline (week 24, p<0.0001). Overall, IP-10 levels decreased during treatment irrespective of intervention or HIV status, with no significant differences between treatment arms at week 24. Notably, IP-10 levels at week 2 predicted rapid sputum culture conversion in the IBU arm, as well as in HIV-negative patients in the ASA arm (AUC: ASA 0.79; IBU 0.76).</p><p><strong>Conclusion: </strong>IP-10 levels measured in DBS are associated with disease severity and treatment response and may serve as a biomarker for therapy monitoring and early prediction of microbiological outcomes in TB, irrespective of adjunctive host-directed therapies. These findings require validation in larger patient cohorts before the method can be implemented in clinical practice.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1924239"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamine metabolic reprogramming in acute and chronic kidney diseases: mechanistic insights and therapeutic implications.","authors":"Ruotong Xu, Jin Zhao, Minna Liu, Yifan Qiao, Xiaoxuan Ning, Shiren Sun","doi":"10.3389/fimmu.2026.1939528","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1939528","url":null,"abstract":"<p><p>Acute kidney injury (AKI) and chronic kidney disease (CKD) are common clinical disorders that have high incidence and mortality. Their pathogenesis and the mechanisms underlying AKI-to-CKD progression remain unclear. Metabolic reprogramming has emerged as a core mechanism driving the onset and progression of kidney diseases. Glutamine (Gln) metabolism, a central component of renal energy metabolism, not only maintains acid-base balance and cellular homeostasis but also actively participates in pathophysiological processes including ischemic injury, oxidative stress, inflammatory regulation and fibrosis. Multi-omics studies have revealed stage-specific alterations in Gln metabolism-associated signatures during kidney injury. In AKI, altered Gln levels and redox-related metabolites may suggest disturbances in metabolic pathways, whereas in CKD, elevated glutaminase 1 (GLS1) expression and glutaminolysis-associated metabolic reprogramming are associated with fibrosis. Gln, as an immunonutrient, also serves as a critical energy substrate to sustain the proliferation, activation, and effector functions of immune cells. Gln metabolism may reshape the immune microenvironment within the injured kidney, thereby modulating disease progression. Targeting the Gln metabolic axis may offer new therapeutic insights for AKI and CKD. However, the changes in Gln metabolism and its consequent immunometabolic effects during the AKI-to-CKD transition remain poorly understood. This narrative review aims to provide a comprehensive overview of the dynamic changes in Gln metabolism during acute and chronic kidney diseases, its stage-specific mechanisms, and its potential as a therapeutic target. We also seek to provide a theoretical basis for developing novel biomarkers and targeted therapies based on Gln metabolic reprogramming.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1939528"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TA-TMA as a clinical model for precision complement therapeutics in stem cell transplantation.","authors":"Sonata Jodele","doi":"10.3389/fimmu.2026.1959683","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1959683","url":null,"abstract":"<p><p>Transplant-associated thrombotic microangiopathy (TA-TMA) has evolved from a poorly understood and frequently fatal complication of hematopoietic stem cell transplantation (HSCT) into the leading clinical model for precision complement therapeutics. Studies of TA-TMA have established endothelial injury and complement dysregulation as clinically actionable mechanisms and demonstrated that successful complement inhibition requires more than selecting an effective therapeutic agent. Longitudinal pharmacokinetic/pharmacodynamic (PK/PD)-guided dosing, durable terminal complement blockade, and integration of biomarkers reflecting complement activation, endothelial injury, inflammation, and organ dysfunction have transformed eculizumab into the first example of individualized complement-directed therapy in transplantation. Beyond improving outcomes in patients with TA-TMA, these advances have fundamentally changed our understanding of post-transplant endothelial injury, revealing shared biological pathways across multiple transplant-associated complications and supporting a transition from syndrome-based to mechanism-based clinical management. The expanding availability of eculizumab biosimilars and complement pathway-specific inhibitors, including lectin pathway inhibition, further broadens opportunities for personalized therapeutic strategies while emphasizing the need for harmonized diagnostic criteria, standardized response assessment, and biomarker-guided patient selection. Together, the lessons learned from TA-TMA provide a framework for future precision complement therapeutics in transplantation and illustrate how mechanistic understanding of disease biology can transform clinical practice.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1959683"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ulvan, carrageenan, and fucoidan: comparative immunomodulatory mechanisms and future directions in major algal sulfated polysaccharides.","authors":"Shuang Zhao, Zhangyi Xia, Jinlin Liu, Meijing Zhang, Maozi Lin, Guangmao Ding, Longchen Tang, Fang Su, Jingyi Sun, Chao Zhao","doi":"10.3389/fimmu.2026.1949951","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1949951","url":null,"abstract":"<p><p>Sulfated polysaccharides derived from marine algae have attracted considerable interest in innate immunity research due to their structural diversity and pronounced immunomodulatory activities. Ulvan, carrageenan, and fucoidan, derived from green, red, and brown algae, respectively, represent three paradigmatic classes of algal sulfated polysaccharides. This review establishes a four-tier analytical framework, namely \"structural features, receptor recognition, signaling pathways, and immune outcomes\", to systematically compare their mechanistic differences in innate immune modulation. This framework provides, for the first time, a unified causal chain from molecular structure to immune effector phenotypes. Ulvan is characterized by coordinated TLR4/cGAS-STING dual pathways: it drives pro-inflammatory responses via the TLR4-MyD88-NF-κB axis while inducing type I interferon production through the cGAS-STING-TBK1-IRF3 cascade. TBK1, as a shared downstream node of both the TLR4-TRIF and cGAS-STING pathways, may mediate signal integration and amplification, thereby conferring a distinctive advantage to ulvan in antiviral immunity. Carrageenan exhibits dual TLR4/NLRP3 activities, with κ/ι/λ subtypes displaying a functional spectrum from localized pro-inflammation to systemic immunostimulation, determined by their sulfate content and gelation properties. A critical distinction must be made between high-molecular-weight native carrageenan (>100 kDa), which is minimally absorbed in the intestine and considered safe, and low-molecular-weight degraded carrageenan (<50 kDa), which carries inflammatory and toxic risks. Fucoidan achieves immunomodulatory pleiotropy through dual TLR4/CLR recognition and concurrent engagement of multiple signaling cascades, encompassing NF-κB-driven pro-inflammation, bidirectional NLRP3 inflammasome regulation, and complement C3 activation. The antiviral effect of fucoidan via the STING pathway, potentially dependent on ROS-mediated DNA damage or endoplasmic reticulum stress, mechanistically differs from ulvan's cGAS-STING activation. The structural basis driving this pathway selectivity resides in an inverse gradient relationship between sulfate and uronic acid contents across the three polysaccharides: sulfate content ranks as fucoidan > carrageenan > ulvan, while uronic acid content follows the opposite order. This inverse gradient serves as the first unified structural principle explaining differential receptor preferences and pathway selection among these three distinct classes of algal polysaccharides. Based on this framework, we propose differentiated polysaccharide design strategies tailored to three therapeutic objectives (pro-inflammation, antiviral defense, and immune balance), offering a roadmap for structure-guided immunomodulation using algal sulfated polysaccharides.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1949951"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-cell metabolic reprogramming in systemic lupus erythematosus: linking intracellular metabolism to effector differentiation and senescent-like/exhausted-like states.","authors":"Yi Zou, Zhichu Ren, Yuki Kudo, Michihito Kono","doi":"10.3389/fimmu.2026.1961063","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1961063","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation and multiorgan inflammation. T-cell metabolic reprogramming has recently emerged as an active area of investigation in the pathogenesis of SLE. This metabolic reprogramming, which involves glycolysis, mitochondrial oxidative phosphorylation, glutamine metabolism, and lipid metabolism, is associated not only with functional alterations in SLE T cells but also with changes in their differentiation and proliferation, potentially contributing to disease pathogenesis and progression. Moreover, metabolic alterations, including mitochondrial dysfunction and reactive oxygen species accumulation, in the context of persistent T-cell activation may contribute to phenotypic transitions toward senescent-like or exhausted-like states. These two partially overlapping but biologically distinct cellular phenotypes may represent divergent cellular responses to chronic inflammatory stimulation. Rather than representing mutually exclusive states or a simple loss of function, both may contribute to the perpetuation of chronic inflammation, immune imbalance and disease activity. This review summarizes recent advances in T-cell metabolic reprogramming in SLE and its potential relationship to senescent-like and exhausted-like T-cell states.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1961063"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal fluid metagenomic next-generation sequencing for culture-negative anaerobic central nervous system infection involving <i>Prevotella oris</i>: attribution challenges in low-biomass specimens.","authors":"Yan Li, Minghua Fan, Yuyuan Hu, Yuhang Yang, Wenyuan Li, Wei Zhang, Yanhong Wang","doi":"10.3389/fimmu.2026.1896093","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1896093","url":null,"abstract":"<p><p>Anaerobic central nervous system (CNS) infections are uncommon but diagnostically difficult because fastidious organisms may be suppressed by empirical antimicrobial therapy and conventional cultures may remain negative. Cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) can recover microbial nucleic acids in this setting, but low microbial biomass creates a central attribution problem: a detected organism may represent active infection, introduced commensal DNA, laboratory background, or bioinformatic misclassification. This narrative Mini Review uses <i>Prevotella oris</i> as a representative oral anaerobe to examine that problem. We synthesize evidence on low-biomass CSF specimen processing and sequencing strategies, including nanopore sequencing, whole-genome amplification, and targeted approaches, alongside contamination control, sequence-level and taxonomic credibility, host-response immunology, neuroimaging and source concordance, antimicrobial timing, and discordant clinical scenarios. We then organize these established principles into an expert-informed two-step pathway that separates technical signal credibility from clinical attribution and explicitly preserves an indeterminate state when evidence conflicts. <i>P. oris</i> is positioned as a useful model of the plausible contaminant paradox rather than as a pathogen with a unique CNS phenotype. We also outline syndrome-based management, source control, and treatment-duration principles. The framework is conceptual and non-validated; its purpose is transparent reasoning and reporting, not diagnostic scoring or probability estimation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1896093"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early dynamics of eosinophils and the neutrophil-to-lymphocyte ratio are associated with severe immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma.","authors":"Ondřej Fiala, Jan Králíček, Jindřich Kopecký, Michal Vočka, Tomas Buchler, Hana Študentová, Jana Obertová, Beáta Rondzíková, Martin Matějů, Dominik Šafčák, Matej Hrnčár, Peter Priester, Martina Spisarová, Anežka Zemánková, Radka Lohynská, Michaela Tkadlecová, Lucie Grmelová, Petr Stránský, Bohuslav Melichar, Patrik Palacka, Alexandr Poprach","doi":"10.3389/fimmu.2026.1944728","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1944728","url":null,"abstract":"<p><strong>Background: </strong>Reliable biomarkers for characterization of the risk of severe immune-related adverse events (irAEs) during immune checkpoint inhibition remain lacking. We hypothesized that early dynamics of complementary complete blood count (CBC)-based immune biomarkers may be associated with severe immune toxicity. We therefore evaluated longitudinal changes in absolute eosinophil count (AEC) and neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.</p><p><strong>Methods: </strong>This multicenter retrospective study included 503 patients with mRCC receiving nivolumab monotherapy in the second or later treatment line. Biomarker analyses were performed using a prespecified 28-day landmark design. AEC and NLR were evaluated at baseline, month 1, and as dynamic Low→High phenotypes, defined as transition from below the baseline upper-quartile threshold to the highest month-1 quartile. Multivariable logistic regression adjusted for age, sex, ECOG performance status, IMDC risk group, and treatment line.</p><p><strong>Results: </strong>Among 501 toxicity-evaluable patients, 57 (11.4%) developed grade 3-4 irAEs. Baseline AEC and NLR were not associated with severe irAEs. In contrast, the AEC Low→High phenotype was associated with severe irAEs after multivariable adjustment (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.02-4.97; P = 0.045), as was the NLR Low→High phenotype (aOR 2.77, 95% CI 1.25-6.17; P = 0.012). In a prespecified combined multivariable model, NLR remained independently associated with severe irAEs (aOR 2.81, 95% CI 1.25-6.30; P = 0.012), whereas the AEC association was attenuated (aOR 2.08, 95% CI 0.90-4.80; P = 0.085).</p><p><strong>Conclusions: </strong>Early dynamics of eosinophils and NLR, rather than baseline biomarker values, were associated with severe irAEs during nivolumab therapy. These findings suggest that eosinophil expansion and inflammatory remodeling may reflect aspects of early immune activation associated with clinically significant immune toxicity. Longitudinal assessment of routinely available CBC-based immune biomarkers therefore warrants prospective validation in cohorts with time-resolved toxicity assessment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1944728"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic stress and macrophage efferocytosis in osteoarthritis: mechanisms and therapeutic implications.","authors":"HaoYang Wu, DeChao Yuan, RenJian He, ShiWei Liu","doi":"10.3389/fimmu.2026.1999085","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1999085","url":null,"abstract":"<p><p>Metabolic disturbances contribute to osteoarthritis through mechanisms that extend beyond increased mechanical loading, yet their effects on inflammatory resolution remain incompletely understood. Macrophage efferocytosis-the recognition, engulfment, and degradation of apoptotic cells-provides a potential link between metabolic stress and persistent synovitis. This Mini Review examines how obesity and hyperglycemia disrupt synovial macrophage clearance and evaluates the rationale for therapeutic restoration. Human observations and experimental osteoarthritis studies implicate reduced growth arrest-specific 6 signaling and hyperglycemia-associated CD11b lactylation in defective apoptotic-cell recognition and uptake. Complementary evidence from other inflammatory conditions identifies membrane trafficking, mitochondrial adaptation, and lysosomal cargo processing as additional determinants of clearance competence. Importantly, glycolysis and lactate have context-dependent effects: although lactylation can impair recognition, adaptive lactate signaling supports repeated engulfment and expansion of pro-resolving macrophages. This distinction challenges indiscriminate glycolytic inhibition and favors interventions matched to the affected clearance step. Defective efferocytosis may amplify synovitis through persistence of cellular debris and loss of resolution-promoting signals, thereby creating an environment unfavorable to cartilage homeostasis. Emerging receptor-directed, metabolic, and intra-articular delivery strategies offer opportunities to restore clearance, but clinical validation remains necessary. Translation will require identification of susceptible macrophage populations, functional assessment of the complete efferocytic process, and demonstration that clearance recovery mediates meaningful improvements in joint structure and symptoms.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1999085"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor-recipient Hepatitis B serological patterns and post-transplant HBV events in pediatric living donor liver transplantation: a single-center retrospective cohort with a nested case series.","authors":"Ying Le, Haifeng Tang, Quanhai Zhang, Jiajun Weng, Lianbin Huang, Xiaoke Dai, Mingman Zhang","doi":"10.3389/fimmu.2026.1977829","DOIUrl":"https://doi.org/10.3389/fimmu.2026.1977829","url":null,"abstract":"<p><strong>Background: </strong>The combined effects of donor hepatitis B core antibody (anti-HBc) status and recipient pre-transplant hepatitis B surface antibody (anti-HBs) levels on post-transplant HBV events remain unclear in pediatric living donor liver transplantation (LDLT).</p><p><strong>Methods: </strong>We retrospectively analyzed pediatric LDLT recipients transplanted between May 2018 and June 2023. The primary outcome was the first post-transplant hepatitis B surface antigen (HBsAg)-positive result, with death treated as a competing event. Recipients were stratified by donor anti-HBc status and recipient anti-HBs level (≥100 vs <100 mIU/mL). Antiviral prophylaxis with entecavir (0.015 mg/kg once daily) was given only to recipients of anti-HBc-positive grafts, and hepatitis B immune globulin was not used. Cumulative incidence was compared using Gray's test, and associated factors were evaluated using Fine-Gray regression.</p><p><strong>Results: </strong>Among 229 recipients, 14 (6.1%) developed HBV events. Events occurred in 0 of 97 recipients with an anti-HBc-negative donor and anti-HBs ≥100 mIU/mL (G1), 3 of 67 with an anti-HBc-negative donor and anti-HBs <100 mIU/mL (G2), 2 of 29 with an anti-HBc-positive donor and anti-HBs ≥100 mIU/mL (G3), and 9 of 36 with an anti-HBc-positive donor and anti-HBs <100 mIU/mL (G4); the corresponding 5-year cumulative incidences were 0%, 4.5%, 6.9% and 25.0% (global Gray's test, P<0.001). Donor anti-HBc positivity (sHR, 8.28; 95% CI, 2.27-30.28; P = 0.001) and recipient anti-HBs <100 mIU/mL (sHR, 6.02; 95% CI, 1.32-27.55; P = 0.021) were independently associated with HBV events, although the wide confidence intervals reflect the small number of events (n = 14) and the magnitude of these estimates should be interpreted with caution.</p><p><strong>Conclusions: </strong>Donor anti-HBc positivity and low recipient pre-transplant anti-HBs were independently associated with post-transplant HBV events after pediatric LDLT. Combined donor-recipient serological stratification identified a clear risk gradient and may support risk-adapted HBV surveillance and prevention.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"17 ","pages":"1977829"},"PeriodicalIF":7.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13696473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}