Biology subjects

Etebar, F.

Publications and source records attributed to Etebar, F..

3 recordsLinked to original sources

bioRxiv2026

Regional and sub-regional microglial heterogeneity in the steady-state mouse brain and retina

CNS-resident immune cells are uniquely adapted to their microenvironment; however, the extent of their regional specialisation remains unclear. We combined morphometric and transcriptomic profiling of microglia across the healthy adult mouse CNS, including the olfactory bulbs, cortex, hippocampus, cerebellum and retina, to define their regional and sub-regional heterogeneity. Bulk RNA-sequencing revealed region-specific signatures, with retinal microglia showing the most divergent transcriptomes, and genes related to antigen presentation, phagocytosis and chemokine signalling among the top differentially expressed genes. Single-cell RNA sequencing identified predominantly homeostatic microglia across all examined regions, alongside smaller clusters of interferon-responsive, chemokine-enriched, apolipoprotein-enriched and proliferative microglia. Apolipoprotein-enriched microglia were restricted to the olfactory bulbs, whereas interferon-responsive microglia were most abundant in the retina. Single-cell profiling of human retinal microglia confirmed clusters enriched for interferon-stimulated genes. Together, this study reveals previously unrecognised microglial heterogeneity within the healthy brain and eye and provides a comparison of microglia transcriptomes across different neuroanatomical regions of the CNS.

immunology↗

bioRxiv2024

Impact of wildfire smoke and diesel exhaust on inflammatory response in aging human microglia

BackgroundAir pollution, particularly from Diesel Exhaust Particles (DEP) and Wildfire Smoke (WFS), is increasingly recognised as a significant driver of neuroinflammation linked to brain diseases. However, the role of microglia in mediating these neuroinflammatory responses remains poorly understood. This study aimed to investigate the effects of air pollution on monocyte-derived microglia-like cells (MDMi) from both young (< 40 years of age), and (older > 60 years of age) healthy individuals, focusing on immune response, cytokine secretion, nitrosative stress, and phagocytic activity. ResultsOur study demonstrated that DEP and WFS extract (WFSE) significantly upregulated expression of the oxidative stress marker, heme-oxygenase-1 (HO-1) in MDMi after 24 hr, with levels normalising by 96 hr, indicating a transient oxidative stress response. Both DEP and WFSE elicited distinct inflammatory cytokine profiles. DEP induced a rapid response, increasing TNF-, IL-6, IL-23, and IL-33 within 2 hr in young MDMi and 24 hr in aged MDMi. In contrast, WFSE triggered a delayed but sustained inflammatory response, with TNF-, IFN-{gamma}, IL-23, and IL-33 levels persisting at 96 hr in aged MDMi, highlighting an age-related vulnerability to air pollutant-induced inflammation. Both pollutants activated p38, ERK, and NF-{kappa}B pathways, with p38 activity resolving by 96 hours and ERK activation persisting, reflecting their distinct roles in cellular stress and inflammation. NF-{kappa}B p65 nuclear translocation, observed at 24 hours, highlighted its critical role in cytokine release and inflammation following exposure to DEP and WFSE. This is the first report of NF-{kappa}B activation in human microglia exposed to air pollutants. ConclusionsThese results highlight the distinct and potentially harmful effects of DEP and WFSE on immune and inflammatory responses in MDMi, particularly in ageing populations, with significant implications for brain health. DEP triggers acute oxidative stress and inflammatory responses, while WFSE induces more prolonged effects, especially in aged microglia. Both pollutants activate the MAPK and NF-{kappa}B pathways and exhibit unique cytokine profiles, underscoring their overlapping yet distinct mechanisms of action. These findings advance our understanding of air pollutant-induced neuroinflammation and its contribution to neurodegeneration, providing a foundation for developing targeted interventions to mitigate the neurotoxic effects of air pollution.

cell biology↗

bioRxiv2024

Tissue-specific immune transcriptional signatures in the bordering tissues of the mouse brain and retina

BackgroundBordering the central nervous system (CNS) parenchyma are the pia mater (the innermost layer of the meninges enveloping the brain) and the choroid (underlying the retina). While near the neural parenchyma, the pia mater and choroid are external to the immune privileged environment of the brain and retina and thus are distinct immune compartments. This study aimed to characterise the transcriptomic signatures of immune cells within the pia mater and choroid bordering the healthy adult mouse CNS. MethodsBrains and eyes were obtained from 7-week-old female C57Bl/6J mice. Pia mater-enriched tissue and choroid were dissected and processed for fluorescence activated cell sorting of CD45+ immune cells and single cell RNA-sequencing. Additionally, single cell RNA-sequencing was performed on immune cells isolated from choroid obtained from human donor eye tissue. Immunostaining and confocal microscopy of wholemount tissue were used to validate selected immune cell populations in situ. ResultsA total of 3,606 cells were sequenced from mouse tissues, including 1,481 CD45+ cells from pia mater-enriched tissue and 2,125 CD45+ cells from choroid. Clustering and differential gene expression analysis revealed heterogeneous subtypes of monocytes/macrophages, dendritic cells, T cells and B cells. While some clusters were common to both pia mater and choroid, others exhibited tissue-specific gene expression profiles and potential functional specialisations. Analysis of 6,501 CD45+ cells sequenced from human choroid identified similar immune cell populations to mouse choroid. ConclusionsThis study provides a detailed characterisation of the molecular signatures of immune cells within the vascular connective tissues bordering the healthy brain and retina, and their potential roles in immune protection.

immunology↗