Oxford open immunology最新文献

{"title":"Decoding sex differences in human immunity through systems immunology.","authors":"Joan Escrivà-Font, Tianze Cao, Camila Rosat Consiglio","doi":"10.1093/oxfimm/iqaf006","DOIUrl":"10.1093/oxfimm/iqaf006","url":null,"abstract":"<p><p>Immune function varies widely across humans. Biological sex is a key factor underlying human immune variability, with men presenting with more severe infections and increased cancer rates, while women exhibit higher vaccine responses and prevalence of autoimmunity. Intrinsic biological sex differences arise from varying contributions of chromosomal sex, and sex hormone sensing and downstream signaling to different cell types. This complex regulation presents a unique opportunity for the exploration of human immune sex differences using systems-level methods of investigation. Here we analyze the current literature and the applications of systems immunology in elucidating the immune sex differences in humans. We examine mechanisms of biological sex modulation of human immunity via sex chromosomes, and particularly emphasize the role of sex hormones. We then focus on how systems immunology has been advancing our understanding of how sex impacts the healthy immune system at steady state, ranging from cell composition, transcriptomics, epigenomics, metabolomics, spatial and cell-cell interactions, to plasma proteomics. We also examine systems-level applications to investigating sex differences upon immune perturbations and give an overview of key future directions for the field. Systems immunology provides a powerful framework to decode biological sex-regulated pathways in immunity, paving the way for more precise, sex-informed therapeutic interventions to address sex differences in immune-related conditions.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"6 1","pages":"iqaf006"},"PeriodicalIF":0.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET in the characterization of immune diseases and development of therapeutics.","authors":"Natasha Patel, Mats Bergstrom, Philip S Murphy, Juliana Maynard","doi":"10.1093/oxfimm/iqaf005","DOIUrl":"10.1093/oxfimm/iqaf005","url":null,"abstract":"<p><p>The immune system is a complex network of cells, tissues and organs that protects the body against harmful pathogens. Characterization of the immune system is essential for understanding the complex interactions underlying pathophysiology and providing insights to enable therapeutic targeting for modern drug development. Tissue and peripheral sampling report on important biomarkers, but may not adequately sample complex, heterogeneous systemic diseases. Imaging has been extensively used in the study of immune diseases, largely relying upon structural measurements of disease manifestation (e.g. X-ray for joint space narrowing in rheumatoid arthritis). These measurements are downstream from drug action, offering no insight into the intricacies of the immune system. Molecular imaging, particularly through Positron Emission Tomography has the potential to map the immune system at the whole-body level, providing non-invasive, quantitative readouts. Adoption of PET clinically and for drug development purposes for studying immune processes has been limited to date, lagging use in neuroscience and oncology. Emerging technical developments are likely to create new opportunities for immune system monitoring: (i) A broad set of clinical probes to study immune cells and associated processes are in development, (ii) The advent of TotalBody PET able to capture high-sensitivity measurements from all tissues with reduced radiation dose burden. This review explores the potential applications of PET for immune drug development, the technology advancements and suggests how adoption barriers can be overcome. The immune toolset of the future will likely demand an integrated approach, using tissue and peripheral readouts combined with immune-specific imaging.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"6 1","pages":"iqaf005"},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI in optimized cancer treatment: laying the groundwork for interdisciplinary progress.","authors":"Gabriel Kalweit, Evelyn Ullrich, Joschka Boedecker, Roland Mertelsmann, Maria Kalweit","doi":"10.1093/oxfimm/iqaf004","DOIUrl":"10.1093/oxfimm/iqaf004","url":null,"abstract":"<p><p>The molecular complexity of cancer presents significant challenges to traditional therapeutic approaches, necessitating the development of innovative treatment strategies capable of addressing the disease's dynamic nature and resistance mechanisms. Data-driven methodologies, particularly those employing Artificial Intelligence (AI), hold substantial promise by advancing a comprehensive understanding of the intricate molecular and cellular mechanisms underlying cancer and supporting the development of adaptive, patient-specific therapeutic strategies. Initiated through the Mertelsmann Foundation, the Collaborative Research Institute Intelligent Oncology (CRIION) in Freiburg im Breisgau, Germany, aims to drive progress in AI-driven oncology. CRIION fosters global collaboration through initiatives like the Intelligent Oncology Symposium and supports multidisciplinary projects designed to integrate AI innovations into clinical workflows.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"6 1","pages":"iqaf004"},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide-specific natural killer cell receptors.","authors":"Malcolm J W Sim, Beining Li, Eric O Long","doi":"10.1093/oxfimm/iqaf003","DOIUrl":"https://doi.org/10.1093/oxfimm/iqaf003","url":null,"abstract":"<p><p>Class I and II human leukocyte antigens (HLA-I and HLA-II) present peptide antigens for immunosurveillance by T cells. HLA molecules also form ligands for a plethora of innate, germline-encoded receptors. Many of these receptors engage HLA molecules in a peptide sequence independent manner, with binding sites outside the peptide binding groove. However, some receptors, typically expressed on natural killer (NK) cells, engage the HLA presented peptide directly. Remarkably, some of these receptors display exquisite specificity for peptide sequences, with the capacity to detect sequences conserved in pathogens. Here, we review evidence for peptide-specific NK cell receptors (PSNKRs) and discuss their potential roles in immunity.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"6 1","pages":"iqaf003"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-seq based T cell repertoire extraction compared with TCR-seq.","authors":"Linoy Menda Dabran, Alona Zilberberg, Sol Efroni","doi":"10.1093/oxfimm/iqaf001","DOIUrl":"10.1093/oxfimm/iqaf001","url":null,"abstract":"<p><p>The purpose of this study is to evaluate the feasibility of using RNA sequencing data as substrate for the computational extraction of T cell receptor sequences. Data from hundreds of thousands of samples is available as RNA sequencing. However, the use of these data for repertoires has not been contrasted against a gold standard. We conducted a benchmarking analysis, comparing T cell receptor data extracted from RNA sequencing to those obtained from T cell receptor sequencing (as gold standard) of the same tissue samples. The focus was on the extraction of Complementarity-Determining Region 3 (CDR3) sequences. To evaluate the influence of sequencing read lengths, samples were analyzed using both 75 base pair single-end and 150 base pair paired-end sequencing methods. In addition we calculated T cell abundance in these samples to test for any correlation between reads and abundance. The findings reveal a significant, perhaps too great, discrepancy between the ability to extract Complementarity-Determining Region 3 sequences from RNA sequencing data and the results obtained from TCR sequencing. The lack of significant improvement with longer read lengths, combined with the absence of correlation to T cell abundance, emphasize the necessity of using T cell receptor sequencing methodologies.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"6 1","pages":"iqaf001"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal-associated invariant T (MAIT) cell responses in <i>Salmonella enterica</i> serovar Typhi strain Ty21a oral vaccine recipients.","authors":"Shubhanshi Trivedi, Olivia J Cheng, Ben J Brintz, Richelle C Charles, Daniel T Leung","doi":"10.1093/oxfimm/iqaf002","DOIUrl":"https://doi.org/10.1093/oxfimm/iqaf002","url":null,"abstract":"<p><p>Mucosal-associated invariant T (MAIT) cells are unconventional innate-like T cells abundant in human mucosal tissues and are associated with protective responses to microbial infections. MAIT cells have the capacity for rapid effector functions, including the secretion of cytokines and cytotoxic molecules. In this study, we examined the longitudinal circulating MAIT cell response to the live attenuated oral vaccine Ty21a (Ty21a) against <i>Salmonella enterica</i> serovar Typhi (<i>S</i>. Typhi). We enrolled healthy adults who received a course of oral live-attenuated <i>S.</i> Typhi strain Ty21a vaccine and assessed peripheral blood MAIT cell longitudinal responses pre-vaccination, and at seven days and one-month post-vaccination, using flow cytometry, cell migration, and tetramer decay assays. We showed that following vaccination, circulating MAIT cells were lower in frequency, but were more activated, and had higher levels of gut-homing marker integrin α4β7 and chemokine receptors CCR9 and CCR6, suggesting the potential of MAIT cells to migrate to mucosal sites. We found no significant differences in MAIT cell functionality, cytotoxicity and T-cell receptor avidity, except in TNF expression, which was higher post-vaccination. We show that MAIT cell immune responses are modulated post-vaccination against <i>S.</i> Typhi. This study contributes to our understanding of MAIT cells' potential role in oral vaccination against bacterial mucosal pathogens.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"6 1","pages":"iqaf002"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144032071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of cryopreservation on immune cell metabolism as measured by SCENITH.","authors":"Curtis Luscombe, Eben Jones, Michaela Gregorova, Nicholas Jones, Laura Rivino","doi":"10.1093/oxfimm/iqae015","DOIUrl":"10.1093/oxfimm/iqae015","url":null,"abstract":"<p><p>The dynamic functioning of immune cells is regulated by cellular metabolic processes, and there is growing interest in the study of immunometabolic correlates of dysfunctional immune responses. SCENITH is a novel flow cytometry-based technique that allows for <i>ex vivo</i> metabolic profiling of immune cells within heterogeneous samples. Cryopreservation of clinical samples is frequently undertaken to facilitate high throughput processing and longitudinal analyses of immune responses, but is thought to lead to cellular metabolic dysfunction. We aimed to investigate the impact of cryopreservation on immune cell metabolism, harnessing SCENITH's unique ability to describe the divergent bioenergetic characteristics of distinct immune cell subsets. We demonstrate that upon activation, T cells are unable to sufficiently/readily undergo metabolic reprogramming. Additionally, we find that cryopreservation introduces a time-dependent metabolic artefact that favours glycolysis and impairs oxidative phosphorylation, suggesting that cryopreservation results in mitochondrial dysfunction. Despite this artefact, SCENITH was still able to reveal the distinct bioenergetic profiles of contrasting immune cells populations following cryopreservation. Whilst SCENITH can provide valuable information about immune cell metabolism even in cryopreserved samples, our findings have important implications for the design of future studies. Investigators should carefully consider how to process and store clinical samples to ensure that cryopreservation does not confound analyses, particularly where longitudinal sampling is required.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"6 1","pages":"iqae015"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-depth characterization of T cell responses with a combined Activation-Induced Marker (AIM) and Intracellular Cytokine Staining (ICS) assay.","authors":"Yeji Lee, Alison Tarke, Alba Grifoni","doi":"10.1093/oxfimm/iqae014","DOIUrl":"10.1093/oxfimm/iqae014","url":null,"abstract":"<p><p>Since T cells are key mediators in the adaptive immune system, evaluating antigen-specific T cell immune responses is pivotal to understanding immune function. Commonly used methods for measuring T cell responses include Activation-Induced Marker (AIM) assays and Intracellular Cytokine Staining (ICS). However, combining these approaches has rarely been reported. This study describes a combined AIM + ICS assay and the effect of collecting the supernatant. Peripheral blood mononuclear cells (PBMCs) from seven healthy donors were stimulated with DMSO (negative control), Epstein-Barr virus (EBV) peptide pools, and PHA (positive control). The AIM markers OX40 + CD137+ were used for CD4+ T cells and CD69 + CD137+ and CD107a + CD137+ for CD8+ T cells. Cytokine-secreting cells were identified as CD40L+ cytokine+ for CD4+ and CD69+ or CD107 + cytokine+ for CD8+ T cells. Half of the supernatant was collected before adding the BFA/Monensin/CD137 antibody solution to assess the impact on T cell responses. The CD107a + CD137+ AIM markers combination had a lower background than CD69 + CD137+, making CD107a+ a more sensitive marker for CD8+ AIM markers. Collecting half of the supernatant did not significantly affect the immune responses. Our AIM + ICS combined protocol enables the simultaneous assessment of activation and cytokine release reducing the sample volume for testing T cell responses. We also show that collecting half of the supernatant does not significantly interfere with immune responses detection.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae014"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR CLIP: comprehensive reviews on interventional studies using precision recombinant technologies: clinical landmarks, implications, and prospects.","authors":"Swarali Yatin Chodnekar, Zurab Tsetskhladze","doi":"10.1093/oxfimm/iqae013","DOIUrl":"10.1093/oxfimm/iqae013","url":null,"abstract":"<p><p>To consolidate clinical trials that utilized the CRISPR technology to synthesise cures for various genetic diseases as a means to provide a window into the progress made so far while paving the way forward for future research and practices. Systematic review (PROSPERO CRD42023479511). Trials from seven databases' (ClinicalTrials.gov, European Union Clinical Trials Registry, ISRCTN registry, ICTRP/trialsearch.who.int, ChiCTR.org.cn, Clinical Trial Registry India, and Cochrane Library/Trials) inception to 9 March 2024, were considered. Exclusion criteria were unrelated, duplicated, non-English, unavailable full texts, diagnostic studies, correlational studies, observational studies, abstract-only papers, reviews or conference papers. Included studies were appraised using the ten-item CASP tool to assess methodological quality. The review identified 82 RCTs utilizing CRISPR and revealed four main themes: Diseases targeted, Countries of Clinical trials, Type of interventions, and Trial trends over the years. Geographically, the United States and China lead in the number of CRISPR clinical trials, followed by the European Union. However, Africa, Asia, and South America have very few trials. Among disease classes, cancer is the most prevalent focus with 39 studies, followed by monogenetic blood diseases, like Thalassemia and sickle cell anaemia. The biological agent CTX001 and Cyclophosphamide each feature in 11 studies. The peak year for clinical trials was 2018, marked by a significant increase with 16 studies conducted. Despite conducting a comprehensive search, the majority of trials were concentrated in the United States and China. Additionally, potential oversights due to vague titles, English-only studies, and indexing issues may have occurred. Nonetheless, by incorporating data from seven distinct databases, this review significantly contributes to understanding CRISPR's utilization in therapeutic clinical trials, paving the way for future research directions. The review underscores the burgeoning interest in CRISPR-based interventions. Current trials barely tap CRISPR's potential for treating genetic diseases.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae013"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The current understanding of the phenotypic and functional properties of human regulatory B cells (Bregs).","authors":"Nawara Faiza Ahsan, Stella Lourenço, Dimitra Psyllou, Alexander Long, Sushma Shankar, Rachael Bashford-Rogers","doi":"10.1093/oxfimm/iqae012","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae012","url":null,"abstract":"<p><p>B cells can have a wide range of pro- and anti- inflammatory functions. A subset of B cells called regulatory B cells (Bregs) can potently suppress immune responses. Bregs have been shown to maintain immune homeostasis and modulate inflammatory responses. Bregs are an exciting cellular target across a range of diseases, including Breg induction in autoimmunity, allergy and transplantation, and Breg suppression in cancers and infection. Bregs exhibit a remarkable phenotypic heterogeneity, rendering their unequivocal identification a challenging task. The lack of a universally accepted and exclusive surface marker set for Bregs across various studies contributes to inconsistencies in their categorization. This review paper presents a comprehensive overview of the current understanding of the phenotypic and functional properties of human Bregs while addressing the persisting ambiguities and discrepancies in their characterization. Finally, the paper examines the promising therapeutic opportunities presented by Bregs as their immunomodulatory capacities have gained attention in the context of autoimmune diseases, allergic conditions, and cancer. We explore the exciting potential in harnessing Bregs as potential therapeutic agents and the avenues that remain open for the development of Breg-based treatment strategies.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae012"},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}