Extracellular vesicles as precision therapeutics for psychiatric conditions: targeting interactions among neuronal, glial, and immune networks

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 8, 2025

The critical role of the immune system in brain function and dysfunction is well recognized, yet development therapies for psychiatric diseases has been slow due to concerns about iatrogenic deficiencies. These are emphasized by lack objective diagnostic tools psychiatry. A promise resolve this conundrum lies exploitation extracellular vesicles (EVs) that physiologically produced or can be synthetized. EVs regulate recipient cell functions offer potential EVs-based therapies. Intranasal administration enables targeting specific regions functions, thereby facilitating design precise treatments diseases. such requires navigating four dynamically interacting networks: neuronal, glial, immune, EVs. networks profoundly influenced fluid distribution. They crucial homeostasis, cellular intercellular communication. Fluid abnormalities, like edema altered cerebrospinal (CSF) dynamics, disrupt these networks, negatively impacting health. deeper understanding above-mentioned vital creating biomarker panels identify distinct patient subsets with similar neuro-behavioral symptoms. Testing functional pathways biomarkers could lead new therapeutic tools. Regulatory approval will depend on robust preclinical data reflecting progress interdisciplinary areas, which pave way innovative treatments. Highly collaborative teams needed achieve ambitious goals.

Language: Английский

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Lung disease in relation to unique monocyte-macrophage subpopulations induced by combined inhalant endotoxin and collagen-induced arthritis

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 9, 2025

Lung disease is the most overrepresented cause of death in rheumatoid arthritis (RA). Animal studies have demonstrated potentiated autoimmunity, arthritis, and profibrotic/inflammatory lung with a combination airborne exposures collagen-induced (CIA), model that recapitulates features RA-associated interstitial (RA-ILD). As patients RA-ILD demonstrate unique circulating monocyte subpopulations, this study aims to characterize infiltrating monocytes/macrophages mouse determine whether reducing these cells mitigates development disease. Autoimmune-prone DBA/1J mice received intranasal inhalation lipopolysaccharide (LPS) daily for up 5 weeks CIA induction. Experimental groups included Sham (saline injection/saline inhalation), (CIA/saline), LPS (saline/LPS), CIA+LPS (CIA/LPS). was assessed by longitudinal imaging, function measurements, bronchoalveolar lavage fluid, tissues, histopathology. Cell subpopulations were analyzed single cell RNA-sequencing flow cytometry. Intravenous clodronate liposome administration employed reduce monocytes. Longitudinal imaging increased volume tissue density mice. assessment showed reduced compliance airway resistance dual exposure. Unsupervised clustering revealed 16 discrete clusters among experimental robust overlapping characteristics both CIA. By cytometry, exposure induced activated CD11c+CD206+CD11b+MHC Class IIhiCD80+ alveolar macrophages, CD11cmidCD206-CD11b+Ly6Chi(and Ly6Clo)MHC IIhiCD80+CD86+ CD11c-CD11b+Ly6ChiMHC monocytic-like cells. MHC IIhi-expressing across monocyte/macrophage treated more aligned than alone. CIA+LPS-induced CD11c+CD11b+ CD11cmidCD11b+ neutrophils, lymphocytes, inflammatory/pro-fibrotic mediators, expression vimentin citrullinated malondialdehyde acetaldehyde (MAA)-modified proteins/lung autoantigens. The interaction inhalation-induced inflammation autoimmune results associated uniquely inflammatory macrophages. Moreover, depletion monocytes attenuated Whereas macrophage immunophenotype endotoxin exposure, co-exposure modeling renders potentially inform pathogenesis treatment RA-ILD.

Language: Английский

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Unveiling the Emerging Role of Extracellular Vesicle–Inflammasomes in Hyperoxia-Induced Neonatal Lung and Brain Injury

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2094 - 2094

Published: Dec. 18, 2024

Extremely premature infants are at significant risk for developing bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). Although BPD is a predictor of poor outcomes, it currently unknown how contributes to brain injury long-term NDI in pre-term infants. Extracellular vesicles (EVs) small, membrane-bound structures released from cells into the surrounding environment. EVs involved inter-organ communication diverse pathological processes. Inflammasomes large, multiprotein complexes that part innate immune system responsible triggering inflammatory responses cell death. Apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) pivotal inflammasome assembly activating caspase-1. Activated caspase-1 cleaves gasdermin D (GSDMD) release 30 kD N-terminal can form membrane pores, leading lytic death, also known as pyroptosis. cleave pro-IL-1β pro-IL-18 their active forms, which be rapidly through GSDMD pores induce inflammation. Recent evidence has emerged activation inflammasomes associated with neonatal lung injury, inhibition reduces hyperoxia-induced injury. Additionally, multiple studies have demonstrated hyperoxia stimulates lung-derived contain cargos. Adoptive transfer these circulation normal mice rats induces This review focuses on EV–inflammasomes’ roles mediating lung-to-brain crosstalk via EV-dependent EV-independent mechanisms critical BPD, pathogenesis. EV–inflammasomes will discussed potential therapeutic targets

Language: Английский

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Brain–Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs

Biology, Journal Year: 2024, Volume and Issue: 13(12), P. 1056 - 1056

Published: Dec. 16, 2024

Bidirectional communication between the central nervous system (CNS) and peripheral organs tissue has been widely documented in physiological pathological conditions. This relies on bilateral transmission of signaling molecules substances that circulate throughout body reach their target site(s) via blood other biological fluids (e.g., cerebrospinal fluid, lymph). One mechanisms by which these molecular messengers are exchanged is through secretion extracellular vesicles (EVs). EVs known to mediate cell-to-cell delivering molecules, including nucleic acids, proteins, lipids, various bioactive regulators. Moreover, can cross blood–brain barrier (BBB), enabling direct periphery brain. In particular, delivery microRNAs (miRNAs) modulate expression profiles recipient cells, thereby influencing functions. review synthesizes current findings about brain–periphery cross-talk mediated EVs-delivered miRNAs. Although this mechanism definitively shown a few cases, much evidence indirectly indicates it could brain–peripherical organs/tissue communication, especially Therefore, understanding process provide valuable insights for treatment management neurological systemic diseases.

Language: Английский

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