Clinical and experimental immunology最新文献

{"title":"Unravelling the pathogenesis of Eosinophilic Esophagitis from genetic predisposition to environmental triggers.","authors":"Sohail Aziz, Raffaele Pellegrino, Pietro Buono, Mara Creoli, Diego Torre, Claudia Chiantese, Antonio Colucci, Marianna Casertano, Paola Ciamarra, Alessandro Federico, Antonietta Gerarda Gravina, Caterina Strisciuglio","doi":"10.1093/cei/uxaf039","DOIUrl":"10.1093/cei/uxaf039","url":null,"abstract":"<p><p>Eosinophilic Esophagitis (EoE) is a chronic disease primarily driven by immune-mediated pathogenesis, characterized by eosinophil-driven inflammation of the oesophagus, leading to organ dysfunction and fibrosis. Although initially considered a rare disorder, EoE is now recognized as one of the leading causes of food impaction and dysphagia. Advances in knowledge and diagnostic techniques have contributed to its increased detection; however, epidemiologic data suggest that the surge in incidence represents an actual rise in disease prevalence rather than solely increased awareness. The pathogenesis of EoE remains largely unclear, but it is believed to involve a complex interplay of genetic predisposition, environmental factors, diet-derived allergens, and immune dysregulation. A significant role in the pathogenesis of EoE is attributed to environmental and, particularly, food allergens, with mechanisms that extend beyond IgE-mediated pathways, as evidenced by the lack of efficacy of anti-IgE therapies such as omalizumab in clinical trials. A key pathogenic feature is the dysregulated activation of pathways mediated by T-helper type 2 (Th2) lymphocytes. Supporting the role of the Th2 system in EoE inflammation is the demonstrated efficacy of monoclonal inhibitors of interleukin 4 and 13 (i.e. dupilumab), currently the only approved biological therapy for this condition. Additionally, the role of autophagic processes in EoE pathogenesis is becoming increasingly evident. This review aims to provide a concise overview of the key pathogenic mechanisms of EoE and the currently available diagnostic approaches, both invasive and non-invasive, for managing this disorder.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune versatility of oral keratinocytes: from barrier integrity to inflammation control-a mini review.","authors":"César Rivera","doi":"10.1093/cei/uxaf069","DOIUrl":"10.1093/cei/uxaf069","url":null,"abstract":"<p><p>Oral keratinocytes are pivotal to the structural and immunological integrity of the oral mucosa, orchestrating mucosal defense through multifaceted immune functions. This narrative review synthesizes mechanistic insights from primary keratinocyte cultures, in vitro infection models, transcriptomic and proteomic profiling, and immunohistochemical analyses to elucidate their roles in pathogen sensing via pattern recognition receptors, antimicrobial peptide production, cytokine secretion, antigen presentation, immune modulation, and tolerance induction. The review highlights their contributions to innate and adaptive immunity, including the secretion of antimicrobial peptides such as β-defensins and the regulation of T-cell responses through major histocompatibility complex molecules. It also examines their dysregulation in chronic inflammatory conditions, such as oral lichen planus, recurrent aphthous stomatitis, and periodontitis, where altered pattern recognition receptors signaling and barrier dysfunction drive disease progression. These insights underscore the therapeutic potential of targeting keratinocyte-mediated immunity to restore mucosal homeostasis.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Type 2 diabetes is associated with the accumulation of senescent T cells.","authors":"Yang Zheng","doi":"10.1093/cei/uxad079","DOIUrl":"10.1093/cei/uxad079","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral immune biomarkers associated with response to adoptive cell therapy with tumor infiltrating lymphocytes.","authors":"Cecilie Oelvang Madsen, Marta Velasco Santiago, Evelina Martinenaite, Troels Holz Borch, Marco Donia, Inge Marie Svane, Morten Hansen","doi":"10.1093/cei/uxaf010","DOIUrl":"10.1093/cei/uxaf010","url":null,"abstract":"<p><p>Adoptive cell therapy (ACT) with ex-vivo expanded tumor-infiltrating lymphocytes (TILs, TIL-ACT) has shown clinical efficacy in a significant proportion of patients with metastatic melanoma. To further target TIL-ACT toward responsive patients, identifying predictive biomarkers and understanding broader immune dynamics remain critical. This study investigated the peripheral blood immune landscape in 47 patients with metastatic melanoma undergoing TIL-ACT, assessing antitumor reactivity and peripheral immune cell profiles before and after treatment. Responders displayed increased frequency of circulating tumor-reactive cells post-treatment, and higher baseline levels of activated CD57-expressing T cells, serving as potential biomarkers of response. In contrast, persistent high serum levels of interleukin (IL)-6 and IL-8, higher frequencies of CD38-expressing T cells, and regulatory T cells (Tregs) post-treatment, correlated with unfavorable outcomes. These findings contribute to understanding the peripheral immune landscape associated with response to TIL-ACT, offering valuable insights into predictive biomarkers and mechanisms to improve patient selection.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What causes lymphopenia in primary lymphatic anomalies? Implications for understanding lymphocyte homeostasis.","authors":"Julian Pearce, Katty Wadda, Pia Ostergaard, Kristiana Gordon, Sahar Mansour, Derek Macallan","doi":"10.1093/cei/uxaf064","DOIUrl":"10.1093/cei/uxaf064","url":null,"abstract":"","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":"219 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mouse CD8+ T cell subsets differentially generate IL-17-expressing cells in the colon epithelium and lamina propria.","authors":"Cunjin Ge, Qiaoyun Tong, Shihua Zheng, Lei Liu, Lugao Tian, Hesheng Luo","doi":"10.1093/cei/uxae120","DOIUrl":"10.1093/cei/uxae120","url":null,"abstract":"<p><p>Colon-resident CD8+ T cells actively contribute to gut homeostasis and the pathogenesis of inflammatory bowel disease. However, their heterogeneity in generating IL-17-expressing CD8+ T cells, i.e. Tc17 cells, has not been thoroughly revealed. This study aims to characterize the abilities of mouse colonic intraepithelial (IE) and lamina propria (LP) CD8+ T cell subsets to differentiate into Tc17 cells. Using flow cytometry, we found that normal TCRβ+CD4-CD8αα+ cells (CD8αα T cells) and TCRβ+CD4-CD8αβ T cells, (CD8αβ T cells), either IE or LP, expressed abundant granzymes and IFN-γ but minute IL-17A. Under the in vitro Tc17-inducing condition, IE CD8αα T cells showed the weakest Tc17 differentiation ability and LP CD8αβ T cells exhibited the strongest Tc17 differentiation ability, whereas IE CD8αβ T cells and LP CD8αα T cells demonstrated moderate Tc17 differentiation abilities. The expression of IL-6 receptor, TGF-β receptor, TCR signaling indicators, CD161, and IL-23 receptor was low in IE CD8αα T cells, median in IE CD8αβ T cells and LP CD8αα T cells, but high in LP CD8αβ T cells. IE CD8αα T cells weakly induced the expression of chemokines, cytokines, and host defense mediators in colonic epithelial cells while LP CD8αβ T cells showed a robust up-regulatory effect. Furthermore, these colonic CD8+ T cell subsets also exhibited different abilities to generate Tc17 cells in inflamed colons. Collectively, LP CD8αβ T cells have the strongest Tc17 differentiation ability and might play a more significant role than the other subsets in Tc17-mediated immunity or inflammation in the colon.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of autologous patient-derived circulating extracellular vesicles to improve drug delivery in rheumatoid arthritis.","authors":"Ori Moskovitch, Adi Anaki, Tal Caller, Boris Gilburd, Ori Segal, Omer Gendelman, Abdulla Watad, Ruty Mehrian-Shai, Yael Mintz, Shlomo Segev, Yehuda Shoenfeld, Rachela Popovtzer, Howard Amital, Gilad Halpert","doi":"10.1093/cei/uxae101","DOIUrl":"10.1093/cei/uxae101","url":null,"abstract":"<p><p>Recognizing the need for innovative therapeutic approaches in the management of autoimmune diseases, our current investigation explores the potential of autologous extracellular vesicles (EVs), derived from the blood of rheumatoid arthritis patients, to serve as therapeutic vectors to improve drug delivery. We found that circulating EVs derived from arthritic mice (collagen-induced arthritis model) express the joint/synovia homing receptor, αVβ3 integrin. Importantly, both autologous labeled EVs, derived from the blood of arthritic mice (collagen antibody-induced arthritis model) and healthy mice-derived EVs, exhibit targeted migration toward inflamed synovia without infiltrating healthy joints, as demonstrated by an in vivo imaging system. Furthermore, EVs derived from plasma of rheumatoid arthritis patients show an overexpression of αV integrin and are effectively taken up by lipopolysaccharides/tumor necrosis factor alpha (TNFα)-induced activated human synovial cell line in vitro, although interestingly the uptake of healthy EVs was found to be significantly increased. Notably, arthritic mice-derived circulating EVs, strongly express murine glucose transporter 1, which in turn can facilitate their binding to glucose-coated gold nanoparticles (previously shown to be conjugated with drugs for improved drug delivery). The significance of our results, lies in the identification of autologous tissue homing EVs as promising vectors, offering a novel avenue to enhance targeted delivery of anti-inflammatory/rheumatic drugs in rheumatoid arthritis treatment.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-modulatory effects of Spindlin-1 inhibitors.","authors":"Susanne Schiffmann, Marina Henke, Friedemann Weber, Michael J Parnham","doi":"10.1093/cei/uxaf013","DOIUrl":"10.1093/cei/uxaf013","url":null,"abstract":"<p><p>Spindlin-1, a multivalent epigenetic reader, is a new target for cancer therapy. Beside the anticancer effect, modulation of the recognition of methyl marks of histones may impact the immune system, which plays an important role in the anticancer strategy of the human organism. Two Spindlin-1 inhibitors (A366, MS31) were characterized to differentiate between drug and target-specific effects. We performed a comprehensive study regarding the influence of Spindlin-1 inhibition on various immune cells. A366 and MS31 showed immune cell type-dependent cytotoxicity with IC50 values in the ranges of 37-143 µM and 11-3122 µM, respectively, macrophages tending to be less susceptible than lymphocytes. A366 had only minor effects on M1 polarization, whereas MS31 shifted the M1 to a M2 phenotype, as shown by regulated cytokines and surface marker expression. Both A366 and MS31 weakened the polarization of predifferentiated M2 macrophages by reducing surface marker expression, cytokines, and inflammatory markers. A366 and MS31 had no effect on activation and energy metabolism of CD4+ T cells. Interestingly, 5 µM A366 and 2.5 µM MS31 clearly prevented B cell activation, as shown by reduced proliferation, plasmablast formation, and release of immunoglobulins A and G. Additionally, A366 increased energy metabolism in B cells. In conclusion, the inhibition of Spindlin-1 had only minor effects on polarization of macrophages and T cell proliferation but profoundly prevented B cell activation at low concentrations. This suggests that Spindlin-1 inhibitors, while mediating anticancerogenic effects, may also suppress the humoral immune response and increase infection risk.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":"219 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of T-bet expressing B cells in lupus patients indicates a putative prognostic and therapeutic value of these cells for the disease.","authors":"Athanasios Sachinidis, Maria Trachana, Anna Taparkou, George Gavriilidis, Vasileios Vasileiou, Sofoklis Keisaris, Panayotis Verginis, Christina Adamichou, Dimitrios Boumpas, Fotis Psomopoulos, Alexandros Garyfallos","doi":"10.1093/cei/uxaf008","DOIUrl":"10.1093/cei/uxaf008","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether T-bet+ B cells, as well as age-associated B cells/ABCs (CD19 + CD21-CD11c + T-bet+) and double-negative B cells/DN (CD19 + IgD-CD27- CXCR5-T-bet+), serve as prognostic and/or therapeutic tools for systemic lupus erythematosus (SLE) in humans.</p><p><strong>Methods: </strong>Flow cytometry was used for enumerating T-bet+ B cells and ABCs/DN subsets, found in the peripheral blood of 10 healthy donors and 22 active SLE patients. Whole blood assay cultures, combined with in vitro pharmacological treatments, were performed to evaluate the effects of hydroxychloroquine, anifrolumab, and fasudil (a ROCK kinase inhibitor) on T-bet+ B cells' percentage. Moreover, previously published single-cell RNA sequencing (scRNA-seq) data were used in a meta-analysis to allow characterization of genes and pathways associated with the biology of T-bet in B cells.</p><p><strong>Results: </strong>T-bet+ B cells displayed an expansion in SLE patients [1.47 (1.9-0.7) vs 10.85 (37.4-3.6)]. Similarly, both ABCs and DN were found to be expanded. Interestingly, percentages of T-bet+ B cells positively correlated with patients' SLEDAI scores (rs = 0.55, P = 0.007). Cell culture experiments conducted revealed that all three agents tested can deplete T-bet + B cells (without affecting the cell viability of lymphocytes, T cells, and B cells). According to bioinformatics analyses, T-bet is highly expressed in two B-cell clusters with pathogenic characteristics for SLE (designated as atypical memory B cells and activated naïve B cells). These clusters can be targeted for therapeutic interventions.</p><p><strong>Conclusions: </strong>T-bet+ B cells can serve as a putative prognostic biomarker of lupus severity. Circumstantial data suggest that these cells may promote disease pathogenesis and may represent a novel therapeutic target.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of cladribine on intrathecal and peripheral B and plasma cells.","authors":"Kimberley Allen-Philbey, Sophie Stephenson, Gina Doody, Amy MacDougall, Mohammad Aboulwafaali, Francesca Ammoscato, Michael Andrews, Sharmilee Gnanapavan, Gavin Giovannoni, Sofia Grigoriadou, Alaco Hickey, David W Holden, Helen Lock, Maria Papachatzaki, Iman Redha, David Baker, Reuben Tooze, Klaus Schmierer","doi":"10.1093/cei/uxae116","DOIUrl":"10.1093/cei/uxae116","url":null,"abstract":"<p><strong>Introduction: </strong>Cladribine is a deoxyadenosine analogue that can penetrate the blood-brain barrier. It is used to treat multiple sclerosis (MS). However, the mechanistic understanding of the effect of this highly effective therapy on B cells and plasma cells in the central nervous system compartment is limited. The CLADRIPLAS study examined the effect of cladribine on peripheral and intrathecal B and plasma cell biology in people with MS.</p><p><strong>Methods: </strong>Thirty-eight people with progressive MS ineligible for- or rejecting-treatment with licenced therapies were recruited and supplied a baseline lumbar puncture. Those exhibiting gadolinium-enhancing or new/enlarging T2 magnetic resonance imaging lesions and/or elevated neurofilament levels were offered subcutaneous cladribine (Litak®). Seven people were eligible; one person died before treatment, and only five completed the first year of treatment. Twenty-two ineligible people were willing to provide a repeat lumbar puncture 12 months later.</p><p><strong>Results: </strong>The CLADRIPLAS study found no evidence of a difference in the odds of a positive cerebrospinal fluid oligoclonal band result between the cladribine-treated and untreated group. This is probably explained by microarray and in vitro studies, which demonstrated that plasmablasts and notably long-lived plasma cells are relatively resistant to the cytotoxic effect of cladribine compared with memory B cells at physiological concentrations. This was consistent with the loss of intracellular deoxycytidine kinase during antibody-secreting cell differentiation.</p><p><strong>Conclusion: </strong>CLADRIPLAS indicates that cerebrospinal fluid oligoclonal bands are not rapidly eliminated in most people with MS. This may be explained by the relative lack of direct cytotoxic action of cladribine on long-lived plasma cells.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}