Clinical and experimental immunology最新文献

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Investigating T cell-derived extracellular vesicles as biomarkers of disease activity, axonal injury, and disability in multiple sclerosis.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-11 DOI: 10.1093/cei/uxaf003
Jennifer L Zagrodnik, Stephanie N Blandford, Neva J Fudge, Shane T Arsenault, Sarah Anthony, Lillian McGrath, Fraser Clift, Mark Stefanelli, Craig S Moore
{"title":"Investigating T cell-derived extracellular vesicles as biomarkers of disease activity, axonal injury, and disability in multiple sclerosis.","authors":"Jennifer L Zagrodnik, Stephanie N Blandford, Neva J Fudge, Shane T Arsenault, Sarah Anthony, Lillian McGrath, Fraser Clift, Mark Stefanelli, Craig S Moore","doi":"10.1093/cei/uxaf003","DOIUrl":"https://doi.org/10.1093/cei/uxaf003","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the CNS, whereby clinical disease activity is primarily monitored by magnetic resonance imaging (MRI).</p><p><strong>Methods: </strong>Given the limitations associated with implementing and acquiring novel and emerging imaging biomarkers in routine clinical practice, the discovery of biofluid biomarkers may offer a more simple and cost-effective measure that would improve accessibility, standardization, and patient care. Extracellular vesicles (EVs) are nanoparticles secreted from cells under both homeostatic and pathological states, and have been recently investigated as biomarkers in MS. The objectives of this study were to longitudinally measure levels of specific immune cell-derived EVs in MS and provide evidence that EV sub-populations may serve as biomarkers of disease activity, axonal injury, and/or clinical disability.</p><p><strong>Results: </strong>Our results demonstrate that the rate of clinical disability in MS negatively correlates with changes in circulating CD3+ EVs within the plasma. Additionally, numbers of CD4+ EVs decrease in individuals with increasing pNfL levels overtime whereby the magnitude of the pNfL increase negatively correlates with changes in plasma CD4+ and CD8+ EVs. Finally, when applying NEDA-3 criteria to define active versus stable disease, individuals with active disease had significantly elevated CD4+ and CD8+ EVs compared to stable disease.</p><p><strong>Conclusion: </strong>In summary, the analysis of specific immune cell-derived EV subsets may provide a method to monitor disability accumulation, disease activity, and axonal injury in MS, while also providing insights into the pathophysiology and cellular/molecular mechanisms that influence progression.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969818","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}
引用次数: 0
Single-cell analysis of lung epithelial cells reveals age and cell population-specific responses to SARS-CoV-2 infection in ciliated cells.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-09 DOI: 10.1093/cei/uxae118
Raven M Osborn, Christopher S Anderson, Justin R Leach, Chin Yi Chu, Stephen Dewhurst, Thomas J Mariani, Juilee Thakar
{"title":"Single-cell analysis of lung epithelial cells reveals age and cell population-specific responses to SARS-CoV-2 infection in ciliated cells.","authors":"Raven M Osborn, Christopher S Anderson, Justin R Leach, Chin Yi Chu, Stephen Dewhurst, Thomas J Mariani, Juilee Thakar","doi":"10.1093/cei/uxae118","DOIUrl":"https://doi.org/10.1093/cei/uxae118","url":null,"abstract":"<p><strong>Introduction: </strong>The ability of SARS-CoV-2 to evade antiviral immune signaling in the airway contributes to the severity of COVID-19 disease. Additionally, COVID-19 is influenced by age and has more severe presentations in older individuals. This raises questions about innate immune signaling as a function of lung development and age.</p><p><strong>Method: </strong>Therefore, we investigated the transcriptome of different cell populations of the airway epithelium using pediatric and adult lung tissue samples from the LungMAP Human Tissue Core Biorepository. Specifically, lung lobes were digested and cultured into a biomimetic model of the airway epithelium on an air-liquid interface. Cells were then infected with SARS-CoV-2 and subjected to single-cell RNA sequencing. Transcriptional profiling and differential expression analysis were carried out using Seurat.</p><p><strong>Results: </strong>The clustering analysis identified several cell populations: club cells, proliferating epithelial cells, multiciliated precursor cells, ionocytes, and two biologically distinct clusters of ciliated cells (FOXJ1high and FOXJ1low). Interestingly, the two ciliated cell clusters showed different infection rates and enrichment of processes involved in ciliary biogenesis and function; we observed a cell-type-specific suppression of innate immunity in infected cells from the FOXJ1low subset. We also identified a significant number of genes that were differentially expressed in lung cells derived from children as compared to adults, suggesting the differential pathogenesis of SARS-CoV-2 infection in children versus adults.</p><p><strong>Conclusion: </strong>We discuss how this work can be used to identify drug targets to modulate molecular signaling cascades that mediate an innate immune response and begin to understand differences in COVID-19 outcomes for pediatric vs. adult populations.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945589","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}
引用次数: 0
Geographic disparities impacting oral vaccine performance: Observations and future directions.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-08 DOI: 10.1093/cei/uxae124
Rachel M Burke, Sasirekha Ramani, Julia Lynch, Laura V Cooper, Haeun Cho, Ananda S Bandyopadhyay, Carl D Kirkwood, A Duncan Steele, Gagandeep Kang
{"title":"Geographic disparities impacting oral vaccine performance: Observations and future directions.","authors":"Rachel M Burke, Sasirekha Ramani, Julia Lynch, Laura V Cooper, Haeun Cho, Ananda S Bandyopadhyay, Carl D Kirkwood, A Duncan Steele, Gagandeep Kang","doi":"10.1093/cei/uxae124","DOIUrl":"https://doi.org/10.1093/cei/uxae124","url":null,"abstract":"<p><p>Oral vaccines have several advantages compared with parenteral administration: they can be relatively cheap to produce in high quantities, easier to administer, and induce intestinal mucosal immunity that can protect against infection. These characteristics have led to successful use of oral vaccines against rotavirus, polio, and cholera. Unfortunately, oral vaccines for all three diseases have demonstrated lower performance in the highest-burden settings where they are most needed. Rotavirus vaccines are estimated to have >85% effectiveness against hospitalization in children <12 months in countries with low child mortality, but only ~65% effectiveness in countries with high child mortality. Similarly, oral polio vaccines have lower immunogenicity in developing country settings compared with high-resource settings. Data are more limited for oral cholera vaccines, but suggest lower titers among children compared with adults, and, for some vaccines, lower efficacy in endemic settings compared with non-endemic settings. These disparities are likely multifactorial, and available evidence suggests a role for maternal factors (e.g., transplacental antibodies, breastmilk), host factors (e.g., genetic polymorphisms-with the best evidence for rotavirus-or previous infection), and environmental factors (e.g., gut microbiome, coinfections). Overall, these data highlight the rather ambiguous and often contradictory nature of evidence on factors affecting oral vaccine response, cautioning against broad extrapolation of outcomes based on one population or one vaccine type. Meaningful impact on performance of oral vaccines will likely only be possible with a suite of interventions, given the complex and multifactorial nature of the problem and the degree to which contributing factors are intertwined.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945579","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}
引用次数: 0
Neuro-Behçet's disease: an update of clinical diagnosis, biomarkers and immunopathogenesis.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-07 DOI: 10.1093/cei/uxae123
Haoting Zhan, Linlin Cheng, Yongzhe Li
{"title":"Neuro-Behçet's disease: an update of clinical diagnosis, biomarkers and immunopathogenesis.","authors":"Haoting Zhan, Linlin Cheng, Yongzhe Li","doi":"10.1093/cei/uxae123","DOIUrl":"https://doi.org/10.1093/cei/uxae123","url":null,"abstract":"<p><p>Neuro-Behçet's disease (NBD) is a more severe but rare symptom of Behçet's disease (BD), which is mainly divided into parenchymal NBD (p-NBD) involving brain stem, spinal cord, and cerebral cortex. Non-p-NBD manifests as intracranial aneurysm, cerebral venous thrombosis, peripheral nervous system injuries, and mixed parenchymal and non-parenchymal disease. P-NBD is pathologically characterized by perivasculitis presenting with cerebrospinal fluid (CSF) pleocytosis, elevated total protein, and central nervous system (CNS) infiltration of macrophages and neutrophils, which are subdivided into acute and chronic progressive stages according to relapsing-remitting courses and responses to steroids. The diagnosis of NBD depends heavily on clinical features and MRI findings. The lack of laboratory biomarkers has hindered standard diagnostics. CSF IL-6 is the most investigated dimension of NBD and correlates with NBD activity, therapeutic responses, and prognosis. Further investigations have focused on inflammatory biomarkers that reflect the activation of innate and adaptive immune responses. Higher levels of CSF MIF and IAP indicated the activation of macrophages in the CNS; increased IL-17, IL-10, T-bet/GATA-3, and ROR-γt /Foxp3 ratios, marking the disrupted scale of the Th1/Th2 and Th17/Treg axis; and elevated BAFF and IgA/IgM intrathecal synthesis, suggesting that B cells play a dominant role in NBD. CNS destruction and degeneration as a consequence of neuroinflammatory cascades were confirmed by elevated CSF levels of NFL, β2MG, and MBP. Autoantibodies, including anti-STIP-1, anti-Mtch1, anti-B-Crystallin and anti-m-Hsp65, provide substantial evidence for autoimmune essence and underlying microbiological infections in NBD immunopathogenesis. We summarized opinions on the clinical diagnosis, biomarkers, and pathological findings of NBD.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945582","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}
引用次数: 0
A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-04 DOI: 10.1093/cei/uxae121
Hadeil Morsi, Aarnoud Huissoon, Alexandros Grammatikos, Andrew Whyte, Ania Manson, Anjali Ekbote, Anju Sivadasan, Anne Pacita Rosillo Boulton, Archana Herwadkar, Ariharan Anantharachagan, Arthur Price, Cathal Steele, Catherine Stroud, Charu Chopra, Dilani Arnold, Efrem Eren, Elizabeth Cleave, Elizabeth Drewe, Emily Moon, Emily Zinser, Grant Hayman, Hana Alachkar, Harichandana Ghanta, Helen Bourne, Intisar Abdelhakam, John Dempster, Katie Townsend, Kavitha Sooriyakumar, Lorena Lorenzo, Magdalena Dziadzio, Manisha Ahuja, Maria Prasinou, Marina Frleta-Gilchrist, Michael Zhang, Moira Thomas, Pavaladurai Vijayadurai, Prashantha Madhuri Vaitla, Ravishankar Sargur, Richard Herriot, Robert L Yellon, Sai Hurng Kham Murng, Sara Drinkwater, Sarah Denness, Sarah Denman, Shuayb Elkhalifa, Sinisa Savic, Sorena Kiani-Alikhan, Tanya I Coulter, Tariq El-Shanawany, Tasneem Rahman, Tomaz Garcez, Patrick F K Yong, Rashmi Jain
{"title":"A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency.","authors":"Hadeil Morsi, Aarnoud Huissoon, Alexandros Grammatikos, Andrew Whyte, Ania Manson, Anjali Ekbote, Anju Sivadasan, Anne Pacita Rosillo Boulton, Archana Herwadkar, Ariharan Anantharachagan, Arthur Price, Cathal Steele, Catherine Stroud, Charu Chopra, Dilani Arnold, Efrem Eren, Elizabeth Cleave, Elizabeth Drewe, Emily Moon, Emily Zinser, Grant Hayman, Hana Alachkar, Harichandana Ghanta, Helen Bourne, Intisar Abdelhakam, John Dempster, Katie Townsend, Kavitha Sooriyakumar, Lorena Lorenzo, Magdalena Dziadzio, Manisha Ahuja, Maria Prasinou, Marina Frleta-Gilchrist, Michael Zhang, Moira Thomas, Pavaladurai Vijayadurai, Prashantha Madhuri Vaitla, Ravishankar Sargur, Richard Herriot, Robert L Yellon, Sai Hurng Kham Murng, Sara Drinkwater, Sarah Denness, Sarah Denman, Shuayb Elkhalifa, Sinisa Savic, Sorena Kiani-Alikhan, Tanya I Coulter, Tariq El-Shanawany, Tasneem Rahman, Tomaz Garcez, Patrick F K Yong, Rashmi Jain","doi":"10.1093/cei/uxae121","DOIUrl":"https://doi.org/10.1093/cei/uxae121","url":null,"abstract":"<p><strong>Background: </strong>Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterisation of the AAE-C1-INH cohort in UK is required to inform management.</p><p><strong>Objectives: </strong>To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical and treatment profiles of AAE-associated diseases in UK.</p><p><strong>Method: </strong>Retrospective data on 117 AAE-C1-INH patients were collected using a national survey proforma across 25/34 Adult Clinical Immunology and Allergy centres in UK. Other European cohorts were compared.</p><p><strong>Results: </strong>Median age at AAE-C1-INH diagnosis was 65 years with 3.4% of patients diagnosed below 40 years. The median delay in diagnosis was one year. Antifibrinolytics and attenuated androgens showed comparable efficacy as LTP 88.9% and 89.5%, respectively. A haematological disorder was identified in 83.8% AAE-C1-INH patients compared to 3.4% autoimmune diseases. The predominant haematological disorders were splenic marginal zone lymphoma (SZL) 34% followed by MGUS 16%. The severity of angioedema did not depend on the associated disease. Anti-C1INH-autoantibodies testing was limited at 23.1%. Rituximab monotherapy was effective in treating 9/9 SZL and 1/2 MGUS-associated AAE-C1-INH. Rituximab efficacy was independent of anti-C1INH-autoantibodies detection with response in 3/3 seronegative and 4/4 seropositive patients.</p><p><strong>Conclusion: </strong>The diagnosis of AAE-C1-INH should not be overlooked below the age of 40 years. The choice of oral LTP should be informed by propensity to side-effects. B-cell depletion could be considered in treating monoclonal B cell disorder-associated-AAE-C1-INH in the absence of haematological indications. Further studies are required to address the clinical utility of anti-C1INH-autoantibodies.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930715","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}
引用次数: 0
The Potential Of Autologous Patient-Derived Circulating Extracellular Vesicles To Improve Drug Delivery In Rheumatoid Arthritis.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-04 DOI: 10.1093/cei/uxae101
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
{"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":"https://doi.org/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 blood of rheumatoid arthritis (RA) 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 labelled EVs, derived from 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 RA patients show an overexpression of αV integrin and are effectively taken up by LPS/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 glucose transporter 1 (mGLUT1), 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 RA treatment.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mouse CD8+ T cell subsets differentially generate IL-17-expressing cells in the colon epithelium and lamina propria.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2025-01-02 DOI: 10.1093/cei/uxae120
Cunjin Ge, Qiaoyun Tong, Shihua Zheng, Lei Liu, Lugao Tian, Hesheng Luo
{"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":"https://doi.org/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":3.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of Neutrophils in Allergic Disease.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2024-12-26 DOI: 10.1093/cei/uxae126
J Trayer, J M Isaza-Correa, L A Kelly, M Kelleher, J O Hourihane, A Byrne, E J Molloy
{"title":"The Role of Neutrophils in Allergic Disease.","authors":"J Trayer, J M Isaza-Correa, L A Kelly, M Kelleher, J O Hourihane, A Byrne, E J Molloy","doi":"10.1093/cei/uxae126","DOIUrl":"https://doi.org/10.1093/cei/uxae126","url":null,"abstract":"<p><p>Neutrophils are short-lived cells of the innate immune system and represent 50-70% of the circulating leucocytes. Their primary role is antimicrobial defence which they accomplish through rapid migration to sites of inflammation followed by phagocytosis, degranulation and the release of neutrophil extracellular traps (NETosis). While previously considered terminally-differentiated cells, they have been shown to have great adaptability and to play a role in conditions ranging from cancer to autoimmunity. This review focuses on their role in allergic disease. In particular: their role as potential amplifiers of type 1 hypersensitivity reactions leading to anaphylaxis; their involvement in alternative pathways of food and drug allergy; their role in allergic rhinitis and asthma and neutrophil dysfunction in atopic dermatitis. The use of potential biomarkers and therapeutic targets is also discussed with a view to guiding future research.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892592","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}
引用次数: 0
Type I interferon and mitochondrial dysfunction are associated with dysregulated cytotoxic CD8+ T cell responses in juvenile systemic lupus erythematosus.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2024-12-25 DOI: 10.1093/cei/uxae127
Anna Radziszewska, Hannah Peckham, Restuadi Restuadi, Melissa Kartawinata, Dale Moulding, Nina M de Gruijter, George A Robinson, Maryam Butt, Claire T Deakin, Meredyth G Ll Wilkinson, Lucy R Wedderburn, Elizabeth C Jury, Elizabeth C Rosser, Coziana Ciurtin
{"title":"Type I interferon and mitochondrial dysfunction are associated with dysregulated cytotoxic CD8+ T cell responses in juvenile systemic lupus erythematosus.","authors":"Anna Radziszewska, Hannah Peckham, Restuadi Restuadi, Melissa Kartawinata, Dale Moulding, Nina M de Gruijter, George A Robinson, Maryam Butt, Claire T Deakin, Meredyth G Ll Wilkinson, Lucy R Wedderburn, Elizabeth C Jury, Elizabeth C Rosser, Coziana Ciurtin","doi":"10.1093/cei/uxae127","DOIUrl":"https://doi.org/10.1093/cei/uxae127","url":null,"abstract":"<p><p>Juvenile systemic lupus erythematosus (JSLE) is an autoimmune condition which causes significant morbidity in children and young adults and is more severe in its presentation than adult-onset SLE. While many aspects of immune dysfunction have been studied extensively in adult-onset SLE, there is limited and contradictory evidence of how cytotoxic CD8+ T cells contribute to disease pathogenesis and studies exploring cytotoxicity in JSLE are virtually non-existent. Here, we report that CD8+ T cell cytotoxic capacity is reduced in JSLE versus healthy controls, irrespective of treatment or disease activity. Transcriptomic and serum metabolomic analysis identified that this reduction in cytotoxic CD8+ T cells in JSLE was associated with upregulated type I interferon (IFN) signalling, mitochondrial dysfunction, and metabolic disturbances when compared to controls. Greater interrogation of the influence of these pathways on altered cytotoxic CD8+ T cell function demonstrated that JSLE CD8+ T cells had enlarged mitochondria and enhanced sensitivity to IFN-α leading to selective apoptosis of effector memory (EM) CD8+ T cells, which are enriched for cytotoxic mediator-expressing cells. This process ultimately contributes to the observed reduction in CD8+ T cell cytotoxicity in JSLE, reinforcing the growing evidence that mitochondrial dysfunction is a key pathogenic factor affecting multiple immune cell populations in type I IFN-driven rheumatic diseases.</p>","PeriodicalId":10268,"journal":{"name":"Clinical and experimental immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885030","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}
引用次数: 0
Detection of Antibodies to Infliximab in routine care: a 4-year French retrospective study.
IF 3.4 3区 医学
Clinical and experimental immunology Pub Date : 2024-12-23 DOI: 10.1093/cei/uxae122
Daniel Bertin, Jehanne Aghzadi, Nathalie Balandraud, Céline Roman, Mélanie Serrero, Sophie Desplat-Jégo
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