Pub Date : 2025-11-03DOI: 10.1016/j.imlet.2025.107106
Franziska Maria Schmidt , Marta Rizzi
The B cell compartment is maintained by continuous replenishment from hematopoietic stem cells (HSCs) and multipotent progenitors, as well as from B cell precursors. B cell depletion is a common therapeutic approach, not only in the context of B cell malignancies, but also in autoimmunity. The targeted elimination of B cells can be achieved through the use of chimeric antigen receptor (CAR)-T cells or monoclonal antibodies or bispecific antibodies that target both B and NK cells or B and T cells. When B cells are depleted, repopulation from bone marrow precursors occurs within three months to one year, following ontogeny. Nevertheless, prolonged B cell aplasia is observed in some patients and is associated with a progressive reduction of serum immunoglobulins and an increased susceptibility to infections. The mechanisms underlying such defects in B cell replenishment remain to be fully elucidated and studies on human B lymphopoiesis are needed in this context. Mouse models can be helpful in studying mechanisms of B cell development and the role of multiple (B cell-specific) genes in this process; however, they do not always mirror the human developmental dynamics and signals. Hence further tools are needed to study human B lymphopoiesis defects. In this review, we summarize the reported studies and cases of prolonged B cell aplasia following B cell depletion and discuss potential underlying causes. We then provide a comprehensive overview of the various in vitro models that can be used to study the dynamic of B lymphopoiesis to dissect B cell developmental defects in humans.
{"title":"Human B-lymphopoiesis: Clinical challenges in B cell reconstitution and advances in in vitro modeling","authors":"Franziska Maria Schmidt , Marta Rizzi","doi":"10.1016/j.imlet.2025.107106","DOIUrl":"10.1016/j.imlet.2025.107106","url":null,"abstract":"<div><div>The B cell compartment is maintained by continuous replenishment from hematopoietic stem cells (HSCs) and multipotent progenitors, as well as from B cell precursors. B cell depletion is a common therapeutic approach, not only in the context of B cell malignancies, but also in autoimmunity. The targeted elimination of B cells can be achieved through the use of chimeric antigen receptor (CAR)-T cells or monoclonal antibodies or bispecific antibodies that target both B and NK cells or B and T cells. When B cells are depleted, repopulation from bone marrow precursors occurs within three months to one year, following ontogeny. Nevertheless, prolonged B cell aplasia is observed in some patients and is associated with a progressive reduction of serum immunoglobulins and an increased susceptibility to infections. The mechanisms underlying such defects in B cell replenishment remain to be fully elucidated and studies on human B lymphopoiesis are needed in this context. Mouse models can be helpful in studying mechanisms of B cell development and the role of multiple (B cell-specific) genes in this process; however, they do not always mirror the human developmental dynamics and signals. Hence further tools are needed to study human B lymphopoiesis defects. In this review, we summarize the reported studies and cases of prolonged B cell aplasia following B cell depletion and discuss potential underlying causes. We then provide a comprehensive overview of the various <em>in vitro</em> models that can be used to study the dynamic of B lymphopoiesis to dissect B cell developmental defects in humans.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107106"},"PeriodicalIF":2.8,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451722","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}
Pub Date : 2025-10-25DOI: 10.1016/j.imlet.2025.107105
Nan Wang , Xingyue Zheng , Qianzi Ma , Yanlu Che , Wanchao Yang , Zhen Liu , Jingting Wang
<div><h3>Background</h3><div>Hydrogen is known to improve allergic rhinitis. Nasal microbiota that are different from those of healthy normal subjects have been detected in the nasal cavity of patients with allergic rhinitis (AR), and the microbiota can influence the metabolic levels of both themselves and their hosts. In addition, hydrogen has been shown to affect microbiota distribution and diversity. These findings suggest that hydrogen may target the nasal microbiota and metabolites to treat AR. Therefore, further in-depth exploration of the specific mechanism of action of hydrogen in the treatment of allergic rhinitis is necessary to provide a more scientific and effective program for the treatment of this disease. In this study, 35 patients with allergic rhinitis were selected as the experimental group, namely the HI group, and 35 healthy individuals were selected as the control group, namely the HC group.</div></div><div><h3>Methods</h3><div>The serum eosinophil count (EOS), immunoglobulin E (IgE) concentration, visual analogue scale (VAS) score, total nasal symptom score (TNSS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used before and after hydrogen inhalation in AR patients. The skin prick test (SPT) was used to determine allergen sensitization. The community composition and relative abundance of the nasal microbiota were examined before and after hydrogen inhalation and in healthy subjects via 16S rRNA gene sequencing. Liquid chromatography‒mass spectrometry (LC‒MS) was used to explore the metabolic profile.</div></div><div><h3>Results</h3><div>There were no adverse reactions during or after hydrogen inhalation in AR patients, and the safety was good, with significant improvements in the VAS, TNSS, EOS, and IgE scores (<em>P</em> < 0.05). The results of 16S rRNA gene sequencing of nasal microbiota revealed that the distribution and diversity of nasal microbiota in AR patients were significantly altered after hydrogen inhalation compared with those before hydrogen inhalation and were closer to those of normal individuals. We also found that the metabolites 19(<em>R</em>)‑hydroxy-prostaglandin E2, arachidonic acid (AA), LEP 20:2, LEP O-18:2, LEP O-22:3, LPS 18:1, and LPS 20:3 were significantly more abundant than normal in nasal secretions in AR and then significantly decreased and approached normal levels after being modulated by hydrogen. 19(<em>R</em>)-Hydroxy-prostaglandin E2 levels were positively correlated with the abundance of Devosia, Paenibacillus, and colonies in the nasal cavity. AA was significantly positively correlated with Muribaculum bacteria and negatively correlated with [Eubacterium]_ruminantium_group. LPE was positively correlated with the bacteria Paenibacillus and Muribaculum and negatively correlated with [Eubacterium]_ruminantium_group. LPS was negatively correlated with [Eubacterium]_ruminantium_group and UCG-002 and positively correlated with Devosia and Muribaculum.</div></div><div><
{"title":"Hydrogen therapy modulates nasal microbiota and metabolites in allergic rhinitis patients","authors":"Nan Wang , Xingyue Zheng , Qianzi Ma , Yanlu Che , Wanchao Yang , Zhen Liu , Jingting Wang","doi":"10.1016/j.imlet.2025.107105","DOIUrl":"10.1016/j.imlet.2025.107105","url":null,"abstract":"<div><h3>Background</h3><div>Hydrogen is known to improve allergic rhinitis. Nasal microbiota that are different from those of healthy normal subjects have been detected in the nasal cavity of patients with allergic rhinitis (AR), and the microbiota can influence the metabolic levels of both themselves and their hosts. In addition, hydrogen has been shown to affect microbiota distribution and diversity. These findings suggest that hydrogen may target the nasal microbiota and metabolites to treat AR. Therefore, further in-depth exploration of the specific mechanism of action of hydrogen in the treatment of allergic rhinitis is necessary to provide a more scientific and effective program for the treatment of this disease. In this study, 35 patients with allergic rhinitis were selected as the experimental group, namely the HI group, and 35 healthy individuals were selected as the control group, namely the HC group.</div></div><div><h3>Methods</h3><div>The serum eosinophil count (EOS), immunoglobulin E (IgE) concentration, visual analogue scale (VAS) score, total nasal symptom score (TNSS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used before and after hydrogen inhalation in AR patients. The skin prick test (SPT) was used to determine allergen sensitization. The community composition and relative abundance of the nasal microbiota were examined before and after hydrogen inhalation and in healthy subjects via 16S rRNA gene sequencing. Liquid chromatography‒mass spectrometry (LC‒MS) was used to explore the metabolic profile.</div></div><div><h3>Results</h3><div>There were no adverse reactions during or after hydrogen inhalation in AR patients, and the safety was good, with significant improvements in the VAS, TNSS, EOS, and IgE scores (<em>P</em> < 0.05). The results of 16S rRNA gene sequencing of nasal microbiota revealed that the distribution and diversity of nasal microbiota in AR patients were significantly altered after hydrogen inhalation compared with those before hydrogen inhalation and were closer to those of normal individuals. We also found that the metabolites 19(<em>R</em>)‑hydroxy-prostaglandin E2, arachidonic acid (AA), LEP 20:2, LEP O-18:2, LEP O-22:3, LPS 18:1, and LPS 20:3 were significantly more abundant than normal in nasal secretions in AR and then significantly decreased and approached normal levels after being modulated by hydrogen. 19(<em>R</em>)-Hydroxy-prostaglandin E2 levels were positively correlated with the abundance of Devosia, Paenibacillus, and colonies in the nasal cavity. AA was significantly positively correlated with Muribaculum bacteria and negatively correlated with [Eubacterium]_ruminantium_group. LPE was positively correlated with the bacteria Paenibacillus and Muribaculum and negatively correlated with [Eubacterium]_ruminantium_group. LPS was negatively correlated with [Eubacterium]_ruminantium_group and UCG-002 and positively correlated with Devosia and Muribaculum.</div></div><div><","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107105"},"PeriodicalIF":2.8,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415791","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}
Pub Date : 2025-10-12DOI: 10.1016/j.imlet.2025.107104
Apostolos Taxiarchis , Jovan Antovic , Olav Rooyackers , Gabriel Dumitrescu
This case report analyzes two severe COVID-19 patients without pulmonary embolism, revealing persistently elevated levels of extracellular vesicles (EVs) carrying tissue factor (TF+), complement proteins (C3a+, TCC+), and endothelial markers (CD144+, CD54+). Temporal trends in these EV subpopulations correlated with clinical deterioration, suggesting their role in endothelial injury, complement hyperactivation, and thromboinflammation. Notably, TF+EV dynamics aligned with anticoagulant treatment responses, while MPO+EVs reflected neutrophil activity without thrombotic complications. Despite differences in patient characteristics, these findings propose that patient-specific EV profiles may serve as potential indicators of disease progression, warranting targeted studies to validate their biomarker potential in severe COVID-19.
{"title":"High complement expression on extracellular vesicles in Covid-19 patients without pulmonary embolism leading to death. Case report","authors":"Apostolos Taxiarchis , Jovan Antovic , Olav Rooyackers , Gabriel Dumitrescu","doi":"10.1016/j.imlet.2025.107104","DOIUrl":"10.1016/j.imlet.2025.107104","url":null,"abstract":"<div><div>This case report analyzes two severe COVID-19 patients without pulmonary embolism, revealing persistently elevated levels of extracellular vesicles (EVs) carrying tissue factor (TF+), complement proteins (C3a+, TCC+), and endothelial markers (CD144+, CD54+). Temporal trends in these EV subpopulations correlated with clinical deterioration, suggesting their role in endothelial injury, complement hyperactivation, and thromboinflammation. Notably, TF+EV dynamics aligned with anticoagulant treatment responses, while MPO+EVs reflected neutrophil activity without thrombotic complications. Despite differences in patient characteristics, these findings propose that patient-specific EV profiles may serve as potential indicators of disease progression, warranting targeted studies to validate their biomarker potential in severe COVID-19.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107104"},"PeriodicalIF":2.8,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292173","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}
Pub Date : 2025-10-12DOI: 10.1016/j.imlet.2025.107103
Junpu Cai , Haitao Li , Wenqiang Cui , Mingyu Hou , Huaiqian Bo , Ning Zhang , Yifan Wang , Jingwen Zhu , Caijun Tian
Background
Lipid metabolism is closely associated with the development of sepsis; however, the relationship between specific lipid molecules and sepsis remains unclear, as does the extent to which immune cell traits mediate the effects of lipid levels on critical sepsis.
Objective
The effects of lipids on critical sepsis were examined in this work, along with the potential mediating function of immune cell characteristics in this process, using Mendelian randomization.
Materials and Methods
A comprehensive two-sample Mendelian randomization analysis was conducted using genetic data from a genome-wide association study of 179 lipids, a large-scale genome-wide association study of 731 immune cell traits, and the latest genome-wide association study of critical sepsis. The ratios of immune cell trait indirect and mediating effects were computed using the coefficient product approach.
Results
We identified 4 lipids and 18 immune cell traits that had a negative causal relationship with critical sepsis, and 1 lipid and 13 immune cell traits that had a positive causal relationship with critical sepsis. Herpesvirus entry mediator (HVEM) on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis, accounting for 6.1% of this effect.
Conclusion
Our study confirmed the genetic causal relationship between lipids, immune cell traits, and critical sepsis, highlighting the potential mediating role of HVEM on effector memory CD8+ T cells and providing insights that may aid in the development of strategies for the prevention and treatment of critical sepsis in the clinic.
{"title":"Herpesvirus entry mediator on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis","authors":"Junpu Cai , Haitao Li , Wenqiang Cui , Mingyu Hou , Huaiqian Bo , Ning Zhang , Yifan Wang , Jingwen Zhu , Caijun Tian","doi":"10.1016/j.imlet.2025.107103","DOIUrl":"10.1016/j.imlet.2025.107103","url":null,"abstract":"<div><h3>Background</h3><div>Lipid metabolism is closely associated with the development of sepsis; however, the relationship between specific lipid molecules and sepsis remains unclear, as does the extent to which immune cell traits mediate the effects of lipid levels on critical sepsis.</div></div><div><h3>Objective</h3><div>The effects of lipids on critical sepsis were examined in this work, along with the potential mediating function of immune cell characteristics in this process, using Mendelian randomization.</div></div><div><h3>Materials and Methods</h3><div>A comprehensive two-sample Mendelian randomization analysis was conducted using genetic data from a genome-wide association study of 179 lipids, a large-scale genome-wide association study of 731 immune cell traits, and the latest genome-wide association study of critical sepsis. The ratios of immune cell trait indirect and mediating effects were computed using the coefficient product approach.</div></div><div><h3>Results</h3><div>We identified 4 lipids and 18 immune cell traits that had a negative causal relationship with critical sepsis, and 1 lipid and 13 immune cell traits that had a positive causal relationship with critical sepsis. Herpesvirus entry mediator (HVEM) on effector memory CD8+ T cells mediates the effects of sterol ester (27:1/18:1) levels on critical sepsis, accounting for 6.1% of this effect.</div></div><div><h3>Conclusion</h3><div>Our study confirmed the genetic causal relationship between lipids, immune cell traits, and critical sepsis, highlighting the potential mediating role of HVEM on effector memory CD8+ T cells and providing insights that may aid in the development of strategies for the prevention and treatment of critical sepsis in the clinic.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107103"},"PeriodicalIF":2.8,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292203","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}
Pub Date : 2025-10-10DOI: 10.1016/j.imlet.2025.107102
Piia Karisola , Harri Alenius
Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures across the life course, offering a unifying framework to understand how immune tolerance is shaped or disrupted. Emerging evidence highlights that early-life exposures are particularly critical. Pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development. In contrast, exposures that enhance biodiversity, microbial diversity, pollution-free air, and balanced nutrition support active tolerance development, especially via regulatory T cells. Mechanistic insights point to the barrier–microbiota–immune axis as central pathways linking the environment to allergic outcomes. Translational studies, including biodiversity enrichment interventions, maternal and infant dietary strategies, and microbiome-based therapies, illustrate the potential of exposome-informed approaches to allergy prevention. However, major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology. This review synthesizes current knowledge on how the exposome modulates immune tolerance and outlines future research directions toward precision prevention. A deeper understanding of these interactions is essential to address the rising global allergy burden.
{"title":"Environmental determinants of immune tolerance in asthma and allergy","authors":"Piia Karisola , Harri Alenius","doi":"10.1016/j.imlet.2025.107102","DOIUrl":"10.1016/j.imlet.2025.107102","url":null,"abstract":"<div><div>Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures across the life course, offering a unifying framework to understand how immune tolerance is shaped or disrupted. Emerging evidence highlights that early-life exposures are particularly critical. Pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development. In contrast, exposures that enhance biodiversity, microbial diversity, pollution-free air, and balanced nutrition support active tolerance development, especially via regulatory T cells. Mechanistic insights point to the barrier–microbiota–immune axis as central pathways linking the environment to allergic outcomes. Translational studies, including biodiversity enrichment interventions, maternal and infant dietary strategies, and microbiome-based therapies, illustrate the potential of exposome-informed approaches to allergy prevention. However, major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology. This review synthesizes current knowledge on how the exposome modulates immune tolerance and outlines future research directions toward precision prevention. A deeper understanding of these interactions is essential to address the rising global allergy burden.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107102"},"PeriodicalIF":2.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274512","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}
Physical activity has recently emerged as a promising modulator of antitumor immunity, but the underlying mechanisms are incompletely understood. Here, we review human studies assessing the effects of exercise on the single steps of the cancer-immunity cycle. Interventions were mostly based on acute or continuous high- and moderate-intensity endurance exercise, followed by analyses of immune cell function and serum markers. There is evidence that exercise enhances tumor cell susceptibility to apoptosis and promotes dendritic cell maturation via damage-associated molecular patterns. Catecholamine-mediated NK and CD8+T cell mobilization facilitates trafficking to tumors, further supported by vascular and metabolic changes to the tumor microenvironment. Overall, there is evidence from human studies that exercise improves immune cell effector function at different steps of the cancer-immunity cycle, thereby potentiating antitumor responses. These findings support the integration of structured exercise therapy into cancer care, possibly in combination with immunotherapeutic strategies. Further mechanistic and clinical research is warranted to optimize exercise-based interventions.
{"title":"The cancer-immunity cycle in motion: The effects of exercise on antitumor immunity","authors":"Katharina Leuchte , Maike Trommer , Gitte Holmen Olofsson , Per thor Straten","doi":"10.1016/j.imlet.2025.107101","DOIUrl":"10.1016/j.imlet.2025.107101","url":null,"abstract":"<div><div>Physical activity has recently emerged as a promising modulator of antitumor immunity, but the underlying mechanisms are incompletely understood. Here, we review human studies assessing the effects of exercise on the single steps of the cancer-immunity cycle. Interventions were mostly based on acute or continuous high- and moderate-intensity endurance exercise, followed by analyses of immune cell function and serum markers. There is evidence that exercise enhances tumor cell susceptibility to apoptosis and promotes dendritic cell maturation via damage-associated molecular patterns. Catecholamine-mediated NK and CD8<sup>+</sup> <em>T</em> cell mobilization facilitates trafficking to tumors, further supported by vascular and metabolic changes to the tumor microenvironment. Overall, there is evidence from human studies that exercise improves immune cell effector function at different steps of the cancer-immunity cycle, thereby potentiating antitumor responses. These findings support the integration of structured exercise therapy into cancer care, possibly in combination with immunotherapeutic strategies. Further mechanistic and clinical research is warranted to optimize exercise-based interventions.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107101"},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250915","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}
Pub Date : 2025-10-03DOI: 10.1016/j.imlet.2025.107100
Haixia Ma , Ying Liu , Yuehong Zhu , Guoxin Xu , Xiaoli Xiang , Senlin Xue , Zhicheng Zhang , Cuie Cheng , Fenying Lu , Bin Wang , Yanyun Zhang , Tingwang Jiang
Primary biliary cholangitis (PBC) is a common chronic cholestatic autoimmune liver disease that may progress to liver fibrosis or cirrhosis if not accurately diagnosed and promptly treated. T follicular helper (Tfh) cells and T peripheral helper (Tph) cells, as subsets of T cells that assist B cells in producing antibodies, are closely related to the pathogenesis of autoimmune diseases. This research aims to explore the potential of Tfh and Tph cells as biomarkers for PBC disease progression. We recruited 30 PBC patients, 25 post-hepatitis B cirrhosis (PHBC) patients, and 30 healthy subjects. Both Tfh and Tph cells were significantly enriched in the peripheral blood of PBC patients, and their frequencies were correlated with autoantibody production. Area under the ROC curve (AUC) analysis demonstrated that Tfh and Tph cell frequencies exhibited convergent diagnostic performance with anti-mitochondrial antibody (AMA) in discriminating PBC patients from healthy controls. Furthermore, the frequencies of these cells were positively correlated with liver enzyme levels (ALT, AST, and GGT), suggesting that they may indicate liver and bile duct damage in PBC patients. The frequency of Tfh cells was negatively correlated with total protein (TP) and albumin (ALB) levels, indicating that the increase of Tfh cells was related to the impairment of hepatocyte function. Additionally, the frequencies of Tfh and Tph cells were positively correlated with IgM levels, showing that these cells seem to be involved in the production of immunoglobulins. Together, Tfh and Tph cells can serve as biomarkers for both diagnosing PBC and correlating with disease severity.
{"title":"Profiling of circulating T follicular helper and T peripheral helper cell subsets in patients with primary biliary cholangitis","authors":"Haixia Ma , Ying Liu , Yuehong Zhu , Guoxin Xu , Xiaoli Xiang , Senlin Xue , Zhicheng Zhang , Cuie Cheng , Fenying Lu , Bin Wang , Yanyun Zhang , Tingwang Jiang","doi":"10.1016/j.imlet.2025.107100","DOIUrl":"10.1016/j.imlet.2025.107100","url":null,"abstract":"<div><div>Primary biliary cholangitis (PBC) is a common chronic cholestatic autoimmune liver disease that may progress to liver fibrosis or cirrhosis if not accurately diagnosed and promptly treated. T follicular helper (Tfh) cells and T peripheral helper (Tph) cells, as subsets of T cells that assist B cells in producing antibodies, are closely related to the pathogenesis of autoimmune diseases. This research aims to explore the potential of Tfh and Tph cells as biomarkers for PBC disease progression. We recruited 30 PBC patients, 25 post-hepatitis B cirrhosis (PHBC) patients, and 30 healthy subjects. Both Tfh and Tph cells were significantly enriched in the peripheral blood of PBC patients, and their frequencies were correlated with autoantibody production. Area under the ROC curve (AUC) analysis demonstrated that Tfh and Tph cell frequencies exhibited convergent diagnostic performance with anti-mitochondrial antibody (AMA) in discriminating PBC patients from healthy controls. Furthermore, the frequencies of these cells were positively correlated with liver enzyme levels (ALT, AST, and GGT), suggesting that they may indicate liver and bile duct damage in PBC patients. The frequency of Tfh cells was negatively correlated with total protein (TP) and albumin (ALB) levels, indicating that the increase of Tfh cells was related to the impairment of hepatocyte function. Additionally, the frequencies of Tfh and Tph cells were positively correlated with IgM levels, showing that these cells seem to be involved in the production of immunoglobulins. Together, Tfh and Tph cells can serve as biomarkers for both diagnosing PBC and correlating with disease severity.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107100"},"PeriodicalIF":2.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232481","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}
Pub Date : 2025-10-02DOI: 10.1016/j.imlet.2025.107098
Bruna Estefânia Diniz Frias , Roberta Oliveira Prado , Mariana Gontijo Ramos , Nathália Werneck Cézar de Oliveira , Fernanda Fortes de Araújo , Liliane Martins dos Santos , Camila Gontijo Ramos , Camila Bechara Kallás , Maria Sílvia Laborne Alves de Sousa , Ismael Artur Costa-Rocha , Joaquim Pedro Brito-de-Sousa , Rachel Basques Caligiorne , Marcelo Antônio Pascoal-Xavier , Vanessa Peruhype-Magalhães , Daniel Gontijo Ramos , Andréa Teixeira-Carvalho , Olindo Assis Martins-Filho
This study aimed to characterize biomarkers of therapeutic response in patients with stable vitiligo undergoing the autologous non-cultured keratinocyte/melanocyte transplantation. The approaches performed were systemic analysis evaluated during pre-transplantation/(D0), seven/(D7), and 28 or more/(D28–45) days after the procedure and compartmentalized analysis in epidermal cell suspension (explant). Increased number of pro-inflammatory monocytes and NK-cells was found during the transplantation follow-up in vitiligo patients compared to the control. There were higher numbers of CD8+T-cells and CD4+HLA-DR+T-cells circulating at D28–45 compared to D0, and increased number of CD8+HLA-DR+T-cells at D28–45 compared to D7. Decreased levels of the most pro-inflammatory chemokines/cytokines during post-transplantation kinetics timeline were observed. Integrative analysis demonstrated that patients with unsatisfactory repigmentation presented higher numbers of connections between the blood/skin components at D0. The data suggest differentiated profiles in the dynamics of the hematological/immunological biomarkers, according to the kinetics timeline and the clinical outcome of repigmentation in vitiligo patients.
{"title":"Immunological features driving distinct repigmentation patterns in patients with stable vitiligo submitted to the autologous keratinocyte/melanocyte transplantation","authors":"Bruna Estefânia Diniz Frias , Roberta Oliveira Prado , Mariana Gontijo Ramos , Nathália Werneck Cézar de Oliveira , Fernanda Fortes de Araújo , Liliane Martins dos Santos , Camila Gontijo Ramos , Camila Bechara Kallás , Maria Sílvia Laborne Alves de Sousa , Ismael Artur Costa-Rocha , Joaquim Pedro Brito-de-Sousa , Rachel Basques Caligiorne , Marcelo Antônio Pascoal-Xavier , Vanessa Peruhype-Magalhães , Daniel Gontijo Ramos , Andréa Teixeira-Carvalho , Olindo Assis Martins-Filho","doi":"10.1016/j.imlet.2025.107098","DOIUrl":"10.1016/j.imlet.2025.107098","url":null,"abstract":"<div><div>This study aimed to characterize biomarkers of therapeutic response in patients with stable vitiligo undergoing the autologous non-cultured keratinocyte/melanocyte transplantation. The approaches performed were systemic analysis evaluated during pre-transplantation/(D0), seven/(D7), and 28 or more/(D28–45) days after the procedure and compartmentalized analysis in epidermal cell suspension (explant). Increased number of pro-inflammatory monocytes and NK-cells was found during the transplantation follow-up in vitiligo patients compared to the control. There were higher numbers of CD8<sup>+</sup> <em>T</em>-cells and CD4<sup>+</sup>HLA-DR<sup>+</sup> <em>T</em>-cells circulating at D28–45 compared to D0, and increased number of CD8<sup>+</sup>HLA-DR<sup>+</sup> <em>T</em>-cells at D28–45 compared to D7. Decreased levels of the most pro-inflammatory chemokines/cytokines during post-transplantation kinetics timeline were observed. Integrative analysis demonstrated that patients with unsatisfactory repigmentation presented higher numbers of connections between the blood/skin components at D0. The data suggest differentiated profiles in the dynamics of the hematological/immunological biomarkers, according to the kinetics timeline and the clinical outcome of repigmentation in vitiligo patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"277 ","pages":"Article 107098"},"PeriodicalIF":2.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228437","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}
Pub Date : 2025-10-02DOI: 10.1016/j.imlet.2025.107099
Chibamba Mumba , Nicholas K. Mwale , Victor Mapulanga , Owen Ngalamika
Background
Penile squamous cell carcinoma (PSCC) is the commonest malignancy of the penis, with a higher incidence and poor treatment outcomes in developing countries. T-cell phenotypes have been shown to identify patients who may respond favorably to immune therapy, and also associate with treatment outcomes. This study aimed to determine and compare the tumor and peripheral blood T-cell phenotypes of individuals with PSCC, and whether factors such as smoking and presence of HPV associate with these T-cell phenotypes.
Methods
We conducted a prospective cross-sectional study at the University Teaching Hospital, Lusaka, Zambia. Participants with a histologically-confirmed PSCC were recruited into the study. Socio-demographic information was obtained, and whole blood was collected and subjected to peripheral blood mononuclear cells (PBMCs) isolation. Fresh penile tumors were mechanically and enzymatically digested. CD4 and CD8 cells were sorted from PBMCs and tumor, stained using antibodies against CD3, CD45RO, CCR7, PD-1, CD103 and CD69, and subjected to flow cytometry. Parts of the tumor were subjected to HPV detection, and histological grading and staging.
Results
Twenty-four participants were recruited into the study. The median age was 55.5 years, 45.8 % were smokers, 87.5 % were HIV positive, 62.5 % had high-risk HPV detected in the tumors, and 25 % had advanced-stage disease. There was a significantly higher proportion of naïve cells among CD4 T-cells from PBMCs than tumor (40.2 % vs 3.8 %; p = 0.01). CD4 T cells from the tumor demonstrated a significantly higher proportion of cells expressing CD69 (3.2 % vs 95.9 %; p = 0.0001), CD103 (0.7 % vs 7.3 %; p = 0.0001), and PD-1 (35.5 % vs 92 %; p = 0.0001) than the ones from PBMCs. Tumoral CD8 T-cells had a significantly lower proportion of terminally-differentiated effector cells but higher proportion of central memory cells compared to PBMCs, (7.9 % vs 15.1 %, p = 0.04) and (55 % vs 14.4 %; p = 0.01) respectively. Tumoral CD8 T-cells also had a significantly higher proportion of cells expressing CD69 (96.7 % vs 8.5 %; p = 0.0001), CD103 (22.2 % vs 1.2 %; p = 0.0001), and PD-1 (79.3 % vs 18.8 %; p = 0.0001) when compared to the PBMCs. Early-stage disease was associated with a significantly higher proportion of central memory CD4 T-cells among the PBMCs when compared with advanced stage disease (46.7 % vs 30 %; p = 0.01), while smoking was associated with a significantly higher proportion of tumoral CD8 T-cells expressing the homing marker CD103 (28.2 % vs 17.8 %; p = 0.01).
Conclusion
PSCC tumors demonstrate a higher proportion of primed T-cells with a memory phenotype compared to T-cells in the circulation. T-cells from PSCC tumors also have a higher proportion of cells expressing the immune checkpoint PD-1 and homing markers than those from the circulation.
背景：阴茎鳞状细胞癌（PSCC）是最常见的阴茎恶性肿瘤，在发展中国家发病率较高，治疗效果较差。t细胞表型已被证明可以识别对免疫治疗反应良好的患者，也与治疗结果相关。本研究旨在确定和比较PSCC患者的肿瘤和外周血t细胞表型，以及吸烟和HPV存在等因素是否与这些t细胞表型相关。方法：我们在赞比亚卢萨卡大学教学医院进行了一项前瞻性横断面研究。组织学证实的PSCC参与者被招募到研究中。获得社会人口统计学信息，采集全血并进行外周血单个核细胞（PBMCs）分离。新鲜阴茎肿瘤用机械和酶消化。从pbmc和肿瘤中分离CD4和CD8细胞，用CD3、CD45RO、CCR7、PD-1、CD103和CD69抗体进行染色，并进行流式细胞术检测。部分肿瘤进行HPV检测，并进行组织学分级和分期。结果：24名参与者被纳入研究。中位年龄为55.5岁，45.8%为吸烟者，87.5%为HIV阳性，62.5%为肿瘤中检测到高危HPV， 25%为晚期疾病。外周血淋巴细胞CD4 t细胞中naïve细胞的比例明显高于肿瘤（40.2% vs 3.8%, p=0.01）。来自肿瘤的CD4 T细胞表达CD69 （3.2% vs 95.9%, p=0.0001）、CD103 （0.7% vs 7.3%, p=0.0001）和PD-1 （35.5% vs 92%, p=0.0001）的比例明显高于来自pbmc的细胞。肿瘤CD8 t细胞的终末分化效应细胞比例明显低于PBMCs，而中枢记忆细胞比例明显高于PBMCs，分别为（7.9% vs 15.1%, p=0.04）和（55% vs 14.4%, p=0.01）。与PBMCs相比，肿瘤CD8 t细胞中表达CD69 （96.7% vs 8.5%, p=0.0001）、CD103 （22.2% vs 1.2%, p=0.0001）和PD-1 （79.3% vs 18.8%, p=0.0001）的细胞比例也显著更高。与晚期疾病相比，早期疾病与PBMCs中央性记忆CD4 t细胞比例显著升高相关（46.7% vs 30%, p=0.01），而吸烟与表达归巢标记CD103的肿瘤CD8 t细胞比例显著升高相关（28.2% vs 17.8%, p=0.01）。结论：与循环中的t细胞相比，PSCC肿瘤中具有记忆表型的启动t细胞的比例更高。来自PSCC肿瘤的t细胞也比来自循环的t细胞表达免疫检查点PD-1和归巢标记的细胞比例更高。
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