Biology subjects

Preston, J.

Publications and source records attributed to Preston, J..

5 recordsLinked to original sources

bioRxiv2026

Tissue retention of dendritic cells drives age-associated protective tolerogenic lymphoid structures

Ectopic lymphoid structures are typically associated with chronic tissue inflammation in autoimmunity and cancer, where they can amplify local immune responses. Similar structures arise spontaneously with age, yet their origin and function remain unclear. Here we identify tissue retention of mature migratory conventional dendritic cells (cDCs) as a driver of age-associated lymphoid organization. Mature cDCs accumulated within lymphoid structures in aged human and mouse tissues. We demonstrate that impaired cDC egress or pharmacological cDC expansion induced de novo structures in mice across multiple otherwise homeostatic organs without associated pathology. Strikingly, senescence-associated tissue cues, which promoted a distinct cDC maturation state, were required for lymphoid niche initiation. Unlike inflammatory structures described in disease, these cDC-driven structures preferentially accumulated tissue-adapted regulatory T cells and protected against inflammatory injury, revealing a previously unrecognized regulatory dimension of age-associated lymphoid organization.

immunology↗

bioRxiv2026

Integrated Transcriptomic Profiling Reveals MAPK14-Related Inflammatory Signalling Associated with Postoperative Atrial Fibrillation

Postoperative atrial fibrillation (POAF) affects up to half of patients after cardiac surgery and raises long-term risk of stroke and death. Why only some patients develop it, despite similar surgical exposure, remains poorly understood. We studied a pilot cohort of 20 patients undergoing cardiac surgery in Northwest England, comparing those who developed POAF within four days (n=10) with those who did not (n=10). Circulating plasma RNA was profiled using the NanoString nCounter Cardiovascular Disease panel, and differentially expressed genes were mapped onto protein-protein interaction networks using STRING and Cytoscape. Candidate genes were then validated by RT-qPCR in the same cohort, alongside serial ELISA measurement of plasma MAPK14 protein. Peripheral blood monocyte, neutrophil and total white blood cell counts were also compared between the two groups on postoperative Days 1, 2 and 4. Screening identified MAPK14, COX6C and COX7B as elevated in POAF, with PTPN12 reduced. These genes clustered within a connected inflammatory and stress-response network, and pathway enrichment pointed to immune activation. RT-qPCR confirmed higher MAPK14, COX6C and COX7B expression in POAF patients. Plasma MAPK14 rose after surgery in both groups, with the largest increase in POAF patients on day two, though this did not reach significance. Peripheral blood monocyte counts were significantly higher in POAF patients than in those without POAF at all three postoperative timepoints, whereas neutrophil and total white blood cell counts did not differ significantly between groups. These early findings identify a circulating plasma RNA signature linked to MAPK14-related inflammatory signalling as a candidate marker of POAF susceptibility, warranting confirmation in a larger, adequately powered cohort.

physiology↗

bioRxiv2025

A single MHCII neoepitope mRNA vaccine elicits CD4 T- and B- cell responses promoting endogenous CD8 anti-tumor immunity

Recent progress in therapeutic cancer vaccines has shown promising clinical activity, especially when targeting MHC class I (MHCI) neoantigen-specific CD8+ T cell responses in post-surgical patients. To explore the role of CD4+ T cells in vaccine-dependent tumor rejection, we constructed an mRNA lipoplex vaccine encoding a single MHCII-restricted neoantigen. The vaccine elicited Tfh and Th1 cell responses while decreasing Tregs, leading to rejection of established tumors in mice. IL-21 and IFN-{gamma}, crucial for Tfh and Th1 function respectively, contributed to anti-tumor activity. B cells and neoantigen-specific antibodies were also shown to participate in vaccine efficacy. Additionally, conventional type 1 dendritic cells (cDC1s) were essential for eliciting vaccine-induced CD4+ T cells, and both cDC1s and CD4+ T cells were required to enhance endogenous CD8+ responses, which were crucial for tumor control. Our results suggest that immunizing against MHCII neoantigens alone is sufficient to orchestrate a potent and cooperative immune response against cancer.

immunology↗

bioRxiv2022

Genome-wide association and genomic prediction of growth traits in the European flat oyster (Ostrea edulis)

The European flat oyster (Ostrea edulis) is a bivalve mollusc that was once widely distributed in Europe and represented an important food resource for humans for centuries. Populations of O. edulis experienced a severe decline across their biogeographic range mainly due to anthropogenic activities and disease outbreaks. To restore the economic and ecological benefits of European flat oyster populations, extensive protection and restoration efforts are in place within Europe. In line with the increasing interest in supporting restoration and oyster farming through the breeding of stocks with enhanced performance, the present study aimed to evaluate the potential of genomic selection for improving growth traits in a European flat oyster population obtained from successive mass-spawning events. Four growth-related traits were evaluated: total weight (TW), shell height (SH), shell width (SW) and shell length (SL). The heritability of the growth traits was moderate-low, with estimates of 0.45, 0.37, 0.22, and 0.32 for TW, SH, SW and SL, respectively. A genome-wide association analysis revealed a largely polygenic genetic architecture for the four growth traits, with two distinct QTLs detected on chromosome 4. To investigate whether genomic selection can be implemented in flat oyster breeding at a reduced cost, the utility of low-density SNP panels (down to 100 SNPs) was assessed. Genomic prediction accuracies using the full density panel were high (>0.83 for all traits). The evaluation of the effect of reducing the number of markers used to predict genomic breeding values revealed that similar selection accuracies could be achieved for all traits with 2K SNPs as for a full panel containing 4,577 SNPs. Only slight reductions in accuracies were observed at the lowest SNP density tested (i.e. 100 SNPs), likely due to a high relatedness between individuals being included in the training and validation sets during cross-validation. Overall, our results suggest that the genetic improvement of growth traits in oysters is feasible. Nevertheless, and although low-density SNP panels appear as a promising strategy for applying GS at a reduced cost, additional populations with different degrees of genetic relationship should be assessed to derive estimates of prediction accuracies to be expected in practical breeding programmes.

genetics↗

bioRxiv2019

Organism-wide single-cell transcriptomics of long-lived C. elegans daf-2 mutants reveals tissue-specific reprogramming of gene expression networks

A critical requirement for a systems-level understanding of complex biological processes such as aging is the ability to directly characterize interactions between cells and tissues within a multicellular organism. C. elegans nematodes harboring mutations in the insulin-like receptor daf-2 exhibit dramatically-increased lifespans. To identify tissue-specific biochemical mechanisms regulating aging plasticity, we single-cell sequenced 3-mRNA libraries generated from seven populations of whole day-one adult wild-type and daf-2-/- worms using the 10x ChromiumV1platform. The age-synchronized samples were bioinformatically merged into a single aligned dataset containing 40,000 age-synchronized wild-type and daf-2-/- cellular transcriptomes partitioned into 101 clusters, using unsupervised machine-learning algorithms to identify common cell types. Here we describe the basic features of the adult C. elegans single-cell transcriptome and summarize functional alterations observed in the gene expression profiles of long-lived daf-2-/- worms. Comprehensive methods and datasets are provided. This is the first study to directly quantify cell-specific differential gene expression between two age-synchronized, genetically-distinct populations of multicellular organisms. This novel approach answers fundamental questions regarding tissue-specific regulation of gene expression and helps to establish a foundation for a comprehensive C. elegans single-cell gene expression atlas.

cell biology↗