Oxford open immunology最新文献

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.

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 Salmonella enterica serovar Typhi (S. Typhi). We enrolled healthy adults who received a course of oral live-attenuated S. 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 S. Typhi. This study contributes to our understanding of MAIT cells' potential role in oral vaccination against bacterial mucosal pathogens.

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 ex vivo 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.

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.

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.

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.

Espírito Santo state, in Brazil, is a dengue-endemic region predicted to suffer from an increase in temperature and drought due to climate change, which could affect the areas with active dengue virus transmission. The study objective was modeling climatic factors and climate change effects in zones suitable for dengue virus transmission in Espírito Santo state, Brazil. Data on dengue reports from 2022 were used to determine climatic variables related to spatial distribution. The climate change projections were generated for the 2030s, 2050s, 2070s, and 2090s for three distinct Shared Socioeconomic Pathways: SSP1-2.6, SSP2-4.5 and SSP5-8.5. A maximum entropy algorithm was used to construct the three models and projections, and the results were used to calculate the ensemble mean. Isothermality, the maximum temperature of the warmest month, precipitation of the wettest month, precipitation of the warmest quarter, and annual precipitation impacted the model. Projections indicated a change in areas suitable for dengue virus transmission, varying from -30.44% in the 2070s (SSP1-2.6) to +13.07% in the 2070s (SSP5-8.5) compared to 2022. The coastal regions were consistently suitable in all scenarios. Urbanized and highly populated areas were predicted to persist with active dengue transmission in Espírito Santo state, posing challenges for public health response.

The existence of commensal fungi that reside within the respiratory tract, termed the airway mycobiome, has only recently been discovered. Studies are beginning to characterize the spectrum of fungi that inhabit the human upper and lower respiratory tract but heterogeneous sampling and analysis techniques have limited the generalizability of findings to date. In this review, we discuss existing studies that have examined the respiratory mycobiota in healthy individuals and in those with inflammatory lung conditions such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. Associations between specific fungi and features of disease pathogenesis are emerging but the precise functional consequences imparted by mycobiota upon the immune system remain poorly understood. It is imperative that further research is conducted in this important area as a more detailed understanding could facilitate the development of novel approaches to manipulating the mycobiome for therapeutic benefit.

Protective immunity to opportunistic fungal infections consists of tightly regulated innate and adaptive immune responses that clear the infection. Immune responses to infections of the vaginal mucosa by Candida species are, however, an exception. In the case of vulvovaginal candidiasis (VVC), the inflammatory response is associated with symptomatic disease, rather than that it results in pathogen clearance. As such VVC can be considered an inflammatory disease, which is a significant public health problem due to its predominance as a female-specific fungal infection. Particularly, women with recurrent VVC (RVVC) suffer from a significant negative impact on their quality of life and mental health. Knowledge of the inflammatory pathogenesis of (R)VVC may guide more effective diagnostic and therapeutic options to improve the quality of life of women with (R)VVC. Here, we review the immunopathogenesis of (R)VVC describing several elements that induce an inflammatory arson, starting with the activation threshold established by vaginal epithelial cells that prevent unnecessary ignition of inflammatory responses, epithelial and inflammasome-dependent immune responses. These inflammatory responses will drive neutrophil recruitment and dysfunctional neutrophil-mediated inflammation. We also review the, sometimes controversial, findings on the involvement of adaptive and systemic responses. Finally, we provide future perspectives on the potential of some unexplored cytokine axes and discuss whether VVC needs to be subdivided into subgroups to improve diagnosis and treatment.

[This corrects the article DOI: 10.1093/oxfimm/iqae003.].