David Sancho

UNDERSTANDING THE INFLUENCE OF THE GUT MICROBIOME ON ATHEROSCLEROSIS DEVELOPMENT

Marcos Femenía-Muiña, Iñaki Robles-Vera, Annalaura Mastrangelo, David Sancho

Age-dependent disease tolerance to SARS-CoV-2 infection

Sharad Rastogi, Miguel Mesquita, Diogo Martins Fonseca, Sara B. Salazar et autres

ABSTRACT Disease tolerance limits infectious disease severity through tissue damage control mechanisms that do not target pathogens directly. Here we demonstrate that age-dependent decline in adipose tissue lipolysis compromises disease tolerance to SARS-CoV-2 infection. Young adult mice exhibited robust adipocyte lipolysis and …

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Metabolic support of trained immune responses in myeloid cells

Aitor Jarit-Cabanillas, Gillian Dunphy, Federico Virga, Jan Van den Bossche et autres

Trained immunity (TI) is defined as a form of innate immune memory characterised by a long-lasting ability to develop enhanced responses to a secondary challenge, whether of the same or a different nature than the initial stimulus. This process is mediated by …

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HIF-1α and HIF-2α differentially regulate alveolar macrophage maturation and function

Elena Priego, Irene Adan-Barrientos, Ruth Conde‐Garrosa, Sarai Martínez-Cano et autres

Alveolar macrophages (AMs) reside in the oxygen-rich alveoli, where hypoxia-inducible transcription factor (HIF) subunits are targeted for degradation by the Von Hippel-Lindau protein (pVHL). We previously showed that Vhl-deficient AMs are immature and functionally impaired. Here, we define isoform-specific roles of HIF-1α …

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Mitochondrial complex I activity promotes antigen cross-presentation in dendritic cells

Sofía C. Khouili, Elena Priego, Ignacio Heras‐Murillo, Gillian Dunphy et autres

Mitochondrial metabolism modulates immune cell signaling, yet how individual electron transport chain complexes fine-tune dendritic cell (DC) function remains unclear. Here, we identify mitochondrial complex I (CI) as a critical metabolic checkpoint controlling antigen cross-presentation by DCs in mice. Deficiency of the …

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Polymeric immunoglobulin receptor deficiency attenuates experimental atherosclerosis

Isabel Cerro-Pardo, Belén Picatoste, Irene Raposo-Gutiérrez, Inmaculada Martos-Folgado et autres

Background Polymeric immunoglobulin receptor (PIGR) is a transmembrane protein widely expressed in mucosal epithelial cells that is involved in the transcytosis of the polymeric immunoglobulins IgA and IgM. Recent findings revealed increased plasma PIGR levels in subjects with subclinical atherosclerosis, although its …

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Loss of SHP-1 in CD11c+ cells impairs anti-tumor immunity

Miguel Galán, Elena Hernández‐García, Pablo Munné, Ana Redondo‐Urzainqui et autres

Background Tyrosine kinases and phosphatases regulate protein phosphorylation and maintain cellular homeostasis. The phosphoprotein tyrosine phosphatase SHP-1 (encoded by the Ptpn6 gene) has been proposed as an immune checkpoint in CD8 + T cells in preclinical models, yet its pharmacological inhibition has …

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Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells

Ignacio Heras‐Murillo, Diego Mañanes, Josep Calafell-Segura, Adrián Belinchón García et autres

Activation of conventional dendritic cells (cDCs) favors increased glycolysis-driven lactic fermentation, while oxidative phosphorylation (OXPHOS) links to tolerance. Here, selective targeting of the mitochondrial electron transport chain (ETC) in cDCs uncovers a critical role for OXPHOS in regulating their immunogenicity. Disruption of …

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A type I interferon-mitochondrial axis regulates efferocytosis and interferon-stimulated gene induction in macrophages

Gillian Dunphy, Irene Adán-Barrientos, Irene Fernández-Delgado, Carolina Villarroya-Beltri et autres

Macrophage metabolism is intricately linked to cellular function. Contrasting with Toll-like receptor (TLR) stimulation, cytosolic nucleic acid sensing induced a decrease in mitochondrial membrane potential (MMP) while maintaining mitochondrial respiration. Interferon α/β (IFN-I) receptor (IFNAR) signaling was necessary and sufficient for this …

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ERC-funded proof of concept grant: targeting imidazoline 1-receptor in atherosclerosis

Annalaura Mastrangelo, Iñaki Robles-Vera, David Sancho

Cardiovascular disease (CVD) remains the leading cause of death and disability. Lipid-lowering therapies, particularly statins, have long served as the cornerstone of CVD prevention, effectively reducing cardiovascular risk. However, the overall disease burden remains high. Atherosclerosis develops silently, with studies describing prevalence …

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BATF3 controls the homeostatic maintenance and function of innate-like γδ T cells

Pedro H. Papotto, Elena Hernández‐García, Ángela Zarco-Cuadrillero, Ana Redondo‐Urzainqui et autres

γδ T cells compose an evolutionarily conserved lineage of lymphocytes, with both adaptive- and innate-like characteristics, contributing to tissue homeostasis, immune surveillance, and rapid responses to stress and infection. While their functional diversity and tissue-specific roles are tightly regulated by transcriptional networks, …

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HIF-1α and HIF-2α transcription factors differentially regulate lung alveolar macrophage function

Elena Priego, Irene Adán‐Barrientos, Ruth Conde‐Garrosa, Sarai Martínez-Cano et autres

ABSTRACT Alveolar Macrophages (AMs) reside in the alveoli, where oxygen pressure is high, therefore maintaining an active degradation of hypoxia-inducible transcription factors (HIF) mediated by the Von Hippel-Lindau protein (pVHL) ubiquitin ligase complex. We previously found that Vhl -deficient AMs not sensing …

es, fr (code pays fourni par la source)