Biology subjects

Corrigan, C.

Publications and source records attributed to Corrigan, C..

4 recordsLinked to original sources

bioRxiv2026

Physiological fatty acid uptake reveals spatial and systemic constraints on nutrient accessibility in vivo

Immune cells rely on exogenous fatty acids (FA) for membrane synthesis, bioenergetics and signalling, yet current approaches cannot accurately quantify physiological FA uptake in vivo. Here, we use cyclopropene-tagged fatty acids (cpFA) that, unlike existing FA-uptake tools, are taken up by physiologically relevant mechanisms. We measure FA uptake at single-cell resolution in vivo and uncover a previously unappreciated distinction between nutrient uptake capacity and nutrient accessibility. Although arachidonic acid exhibits the highest uptake capacity ex vivo across immune populations, it displays limited tissue accessibility in vivo, whereas palmitate is broadly accessible. In vivo nutrient-uptake measurements reveal that tissue architecture shapes nutrient accessibility, with spatial constraints in the spleen and exclusion of circulating FA, but not amino acids, from the thymus. Together, these findings identify nutrient accessibility as a distinct layer of metabolic regulation and reveal that immune-cell metabolism is shaped by spatial and systemic constraints on nutrient access HighlightsO_LINutrient accessibility is a distinct layer of metabolic regulation C_LIO_LIPhysiological FA uptake differs from ex vivo uptake capacity C_LIO_LISpatial and systemic factors govern fatty-acid accessibility C_LIO_LITissue context shapes immune-cell metabolism in vivo C_LI In briefUsing bioorthogonal FA to quantify physiological nutrient uptake in vivo, Wang et al. show that nutrient accessibility is distinct from nutrient uptake capacity. Tissue architecture and systemic FA distribution create spatial constraints on nutrient access, revealing an underappreciated layer of metabolic regulation in immune cells.

immunology↗

bioRxiv2026

IgG4⁺ plasma cell enrichment and {lambda}-chain-biased BCR remodeling drive low-grade autoimmunity in chronic obstructive pulmonary disease

BackgroundThis study aimed to elucidate B cell subset pathology in COPD, a poorly characterized area, with a focus on its similarities to and differences from classical autoimmune disorders. MethodsThe single-cell RNA-sequencing (scRNA-seq) data from COPD and autoimmune diseases were obtained from Gene Expression Omnibus (GEO) for comparative analyses of B cell subsets and functions via differentially expressed genes (DEGs), KEGG, protein-protein interaction (PPI), and cell-cell communication analyses. Serum IgG4 was measured by ELISA and correlated with clinical parameters. The peripheral blood B cells were sorted by flow cytometry for single-cell B cell receptor (BCR) sequencing. A v-Abl/Bcl2 pro-B cell line was stimulated with cigarette smoke extract (CSE) to assess abnormal development in vitro. ResultsIn lung tissue, IgG4+ plasma cells were enriched and expressed BCR activation/inflammatory genes and TNF/NF-{kappa}B/MAPK pathways. Serum IgG4 concentrations correlated negatively with pre-and post-bronchodilator FEV1/FVC. B cell interacted with monocytes, macrophages, fibroblasts and endothelial cells via IL-1{beta}/IL-6, integrin and chemokine signalling, contributing to chronic inflammation and remodelling. In peripheral blood, transitional T1 B cells were increased, accompanied by {lambda}-chain enrichment and increased IGLV1-47 usage, as well as enrichment of autoimmune pathways. In the bone marrow, the numbers of pre-B I cells were increased while those of small pre-B III cells were reduced, with altered expression of BCR development genes. CSE stimulation of the pro-B cell line reduced {lambda}5 expression in a concentration-dependent manner. ConclusionsThe autoimmune abnormalities in COPD appear more restricted, although IgG4 antibody generation may contribute to immune-mediated lung damage.

immunology↗

bioRxiv2025

A Novel Cyclopropenyl Fatty Acid Library Reveals Tissue-Specific Preferences for Regulatory T Cell Uptake Through Click-Chemistry

The activation of T-cells is heavily shaped by the nutrients that are available during activation. Fatty acids can have highly pleiotropic effects in this process. On the one hand, they are essential for driving T-cell activation, yet on the other hand they can affect curtailed T-cell activation. These differences are likely dependent on the nature and absolute uptake of the fatty acids. Quantifying the uptake of specific FAs by individual cells and studying the effect on the phenotype of the cell is currently not possible with existing tools. Here we therefore use the live-cell compatible Inverse Electron-Demand Diels-Alder reaction combined with the synthesis of saturated, unsaturated and polyunsaturated fatty acids carrying the 1-carbon cyclopropene click group. Single cell uptake studies of these various clickable FAs in primary immune cell mixtures show highly divergent uptake behaviour between different immune cells, with polyunsaturated fatty acids markedly preferred by all immune cells tested.

immunology↗

bioRxiv2018

Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter.

BackgroundParticulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.\n\nObjectivesMechanistic cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways.\n\nMethodsTranscriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D.\n\nResultsTranscriptome analysis identified over 500 genes significantly perturbed by PM-stimulation, including multiple pro-inflammatory cytokines. Vitamin D altered expression of a subset of these PM-induced genes, including suppressing IL6. Addition of vitamin D suppressed PM-stimulated IL-6 production, although to significantly greater extent in healthy versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, supporting a role for this pathway in the anti-inflammatory actions of vitamin D.\n\nConclusionsIn a study using HBECs from 18 donors, vitamin D enhanced HBEC antioxidant responses and modulated the immune response to PM, suggesting that vitamin D may protect the airways from pathological pollution-induced inflammation.

immunology↗