http://bura.brunel.ac.uk/handle/2438/32873 2026-05-19T19:31:11Z http://bura.brunel.ac.uk/handle/2438/33249 Title: Immune dysregulation in tuberculosis-diabetes comorbidity: mechanistic and translational insights Authors: Saula, AY; Cevik, M; Cliff, JM; Ronacher, K; Bowness, R Abstract: Background: Tuberculosis (TB) remains a leading cause of infectious disease mortality worldwide, and the rising prevalence of diabetes mellitus (DM) represents a major obstacle to TB control. DM increases susceptibility to TB, worsens disease severity, delays treatment response, and is associated with poorer outcomes, largely through disruption of host immunity. Methods: We conducted a systematic review of studies published between 1974 and May 31, 2023 that examined immunological mechanisms through which DM alters TB pathogenesis. In total, 81 eligible studies involving animal models, human participants, or combined approaches were identified and synthesised across different stages of TB. Results: Across studies, DM was associated with broad dysregulation of innate and adaptive immune responses, altered cytokine signalling, impaired granuloma structure and function, and reduced control of Mycobacterium tuberculosis (Mtb). Distinct immune profiles emerged between TB disease with DM and latent TB infection with DM, with heterogeneity partly explained by differences in study design, metabolic status, and disease stage. Importantly, emerging evidence indicates that pre-diabetes and intermediate hyperglycaemia may also compromise TB immunity and contribute to disease progression. Conclusion: Our findings highlight DM as a key immunometabolic modifier of TB pathogenesis. They also suggest that earlier metabolic optimisation and hostdirected therapeutic strategies could be explored as potential approaches to improve outcomes in this growing high-risk TB-DM population. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431040. Description: Data availability statement: The data analyzed in this study is subject to the following licenses/restrictions: The datasets can be shared with researchers upon request. Requests to access these datasets should be directed to Aminat Y. Saula, ays27@bath.ac.uk.; Supplementary material: The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2026.1803046/full#supplementary-material . 2026-04-23T00:00:00Z http://bura.brunel.ac.uk/handle/2438/33179 Title: CAR-mediated release of IL-10 increases the function of regulatory T cells: relevance for future clinical application Authors: Saleem, A; Peng, Q; Tang, Z; Mohseni, YR; Scottà, C; Shangaris, P; Smit, K; Vermeij, WP; Issa, F; Lombardi, G; Fruhwirth, GO Abstract: Regulatory T cell (Treg) therapy emerges for various indications associated with a breakdown of immune tolerance. Antigen-specific chimeric antigen receptor (CAR) Tregs are frontrunners for transplantation and autoimmune diseases and are currently being clinically evaluated. We aimed to link CAR-antigen engagement with immunosuppressive cargo release into the local microenvironment to boost efficacy and reduce side effects. We used our HLA-A∗02 CAR and immunosuppressive interleukin-10 (IL-10) as model components to generate human CAR Tregs that release IL-10 upon CAR engagement. These were compared to CAR Tregs with constitutive or no IL-10 expression by evaluating phenotypes, antigen-specific IL-10 release, and suppression of effector cell proliferation in vitro and performance in vivo in a humanized xenogeneic graft-versus-host disease (xeno-GvHD) model. We demonstrated successful multi-construct engineering of CAR Tregs, which released upon CAR engagement 2.5-fold more IL-10 than CAR Tregs lacking the corresponding antigen-specific IL-10 secretion module. Neither phenotype nor function was affected by expressing this module. In the xeno-GvHD model, we showed the beneficial effect of IL-10 release, particularly evident when compared to constitutive IL-10 expression that impaired CAR-Treg efficacy. We provide first proof-of-principle for engineering human CAR Tregs to release an immunosuppressive cytokine upon CAR engagement. This approach will both enhance the potency of CAR Tregs at the intended target sites and limit their off-target effects. Description: Data and code availability: The data presented here are available on request from the corresponding authors.; Supplemental information is available online at: https://www.sciencedirect.com/science/article/pii/S1525001626000870#appsec2 . 2026-02-06T00:00:00Z http://bura.brunel.ac.uk/handle/2438/33171 Title: Clinical assessment meets laboratory science: adapting OSCE methodology for authentic biosciences evaluation in the age of generative AI Authors: Mann, R; Tosi, S; Tree, D Abstract: The proliferation of generative artificial intelligence (AI) tools has fundamentally challenged traditional written assessments across higher education, with particular implications for laboratory-based disciplines where written work may substitute for demonstration of practical competence, necessitating approaches that prioritise direct performance. This study presents the adaptation of objective structured clinical examination (OSCE) methodology from medical education to laboratory biosciences, demonstrating a practical framework for authentic assessment in the AI era. We describe and evaluate the transformation of a microscopy assessment in FHEQ Level 4 Biomedical Sciences from a traditional laboratory report to a 20-minute OSCE-style practical evaluation. The redesigned assessment maintained grade distributions while eliminating AI vulnerability through real-time performance demonstration and conversational examination. The implementation achieved close alignment between learning outcomes and assessment methods while providing inherent resistance to generative AI exploitation through direct performance requirements. Equity implications are complex and context-dependent, with potential barriers for students with communication differences alongside potential benefits for others, such as those with written communication difficulties, emphasising the importance of balanced assessment portfolios and appropriate reasonable adjustments. The cross-disciplinary adaptation demonstrates that OSCE methodology offers a scalable solution to AI-era assessment challenges, with performance-focused design maintaining academic integrity more effectively than restrictive policies while enhancing authenticity and equity outcomes. Description: Perspective. 2026-03-24T00:00:00Z http://bura.brunel.ac.uk/handle/2438/33116 Title: Single-cell transcriptomics identifies regulatory T cell heterogeneity in gestational diabetes mellitus Authors: Mensah, NE; Efthymiou, A; Mureanu, N; Martín Monreal, MT; Vaikkinen, H; Kannambath, S; Bowman, A; Menon, A; Tree, T; Lombardi, G; Dhami, P; Nicolaides, KH; Scottà, C; Shangaris, P Abstract: Background: Gestational diabetes mellitus (GDM) is a common pregnancy complication associated with hyperglycaemia, chronic inflammation and adverse health outcomes. Regulatory T cells (Tregs) are thought to contribute to GDM due to their role in suppressing inflammation. However, whether specific Treg subsets are transcriptionally dysregulated in patients with GDM remains unclear. Methods: To investigate Treg transcriptional variation in GDM, we applied single-cell RNA sequencing to Tregs and CD4 + T cells isolated from the blood of 13 healthy pregnant women and 10 female patients with GDM. Results: We observed no significant differences in Treg cluster proportions with disease status, however, Memory CD4 + T cells were more abundant in patients diagnosed with GDM, substantiated by mass cytometry. We report Treg subsets altered in GDM, including naive Tregs with reduced expression of AP-1 transcription factor subunits and effector Tregs with increased signalling of genes associated with angiogenesis. Expression levels of genes dysregulated in GDM Tregs were informative of GDM status in pseudobulk, placental and whole blood mRNA from independent cohorts. TXNIP, which regulates glucose levels, emerged as the most significant discriminator of GDM status from bulk mRNA. Conclusions: This study uncovers transcriptional differences of Treg cell subsets from GDM patients and transcriptional markers informative of GDM status. Description: Plain Language Summary: Gestational diabetes mellitus (GDM) is a common pregnancy condition linked to high blood sugar and increased inflammation, which can affect the health of both mother and baby. Immune cells called regulatory T cells (Tregs) help control inflammation, and their activity in a mother’s blood may be linked to GDM. To understand how Tregs behave in patients with GDM, we captured these cells from blood samples of pregnant women diagnosed with GDM and pregnant women without a GDM diagnosis. We profiled the expression of RNA in individual Tregs from these patients. We found that, while overall Treg numbers are similar, the activity of specific genes varies in Tregs from women with GDM. Disrupted RNA levels of one gene related to glucose control (TXNIP) may be an informative marker for GDM in blood. Our findings enhance the understanding of immune changes in GDM and may inform future approaches for early detection and monitoring.; Data availability: Single-cell RNA sequencing data has been submitted to Gene Expression Omnibus (Accession: GSE280975). Bulk RNA sequencing data was downloaded from Gene Expression Omnibus (Accession: GSE154414; GSE92772 - RNA sequencing data of whole blood cells of normal glucose tolerant (NGT) and gestational diabetes (GDM) pregnant women). Data underlying the figures are available on Zenodo [59.] Mensah, N. Single-cell transcriptomics identifies regulatory T cell heterogeneity in Gestational Diabetes Mellitus [Data set]. Zenodo. https://doi.org/10.5281/zenodo.18032075 (2026).; Code availability: R scripts used to perform the analyses are available at GitHub [60.] Mensah, N. E. rutepo_gdm_treg. GitHub repository. https://github.com/NMNS93/rutepo_gdm_treg (2025).; Springer Nature is providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.; Supplementary information is available online at: https://www.nature.com/articles/s43856-026-01563-0#Sec24 . 2026-04-03T00:00:00Z